Some studies have found significant concentrations of aluminum in the brains of PD patients. The following are some abstracts. Authors Leveugle B. Spik G. Perl DP. Bouras C. Fillit HM. Hof PR. Institution Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, NY 10029. Title The iron-binding protein lactotransferrin is present in pathologic lesions in a variety of neurodegenerative disorders: a comparative immunohistochemical analysis. Source Brain Research. 650(1):20-31, 1994 Jul 4. Abstract Lactotransferrin is a glycoprotein that specifically binds and transports iron. This protein is also believed to transport other metals such as aluminum. Several lines of evidence indicate that iron and aluminum are involved in the pathogenesis of many dementing diseases. In this context, the analysis of the iron-binding protein distribution in the brains of patients affected by neurodegenerative disorders is of particular interest. In the present study, the distribution of lactotransferrin was analyzed by immunohistochemistry in the cerebral cortex from patients presenting with Alzheimer's disease, Down syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam, sporadic amyotrophic lateral sclerosis, or Pick's disease. The results show that lactotransferrin accumulates in the characteristic lesions of the different pathologic conditions investigated. For instance, in Alzheimer's disease and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation and inferior temporal cortex. Senile plaques and Pick bodies were also consistently labeled. These staining patterns were comparable to those obtained with antibodies to the microtubule-associated protein tau and the amyloid beta A4 protein, although generally fewer neurofibrillary tangles were positive for lactotransferrin than for tau protein. Neuronal cytoplasmic staining with lactotransferrin antibodies, was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer's disease, Guamanian cases, Pick's disease, and particularly in Down syndrome. Lactotransferrin was also strongly associated with Betz cells and other motoneurons in the primary motor cortex of control, Alzheimer's disease, Down syndrome, Guamanian and Pick's disease cases. These same lactotransferrin-immunoreactive motoneurons were severely affected in the cases with amyotrophic lateral sclerosis. It is possible that in these neurodegenerative disorders affected neurons either take up or synthesize lactotransferrin to an abnormally elevated rate. An excessive accumulation of lactotransferrin, as well as transported iron and aluminum, may lead to a cytotoxic effect resulting in the formation of intracellular lesions and neuronal death. Authors Yasui M. Ota K. Garruto RM. Institution Division of Neurological Diseases, Wakayama Medical College, Japan. Title Concentrations of zinc and iron in the brains of Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia. Source Neurotoxicology. 14(4):445-50, 1993 Winter. Abstract Simultaneous measurements of zinc (Zn) and iron (Fe) concentrations were determined using neutron activation analysis in gray and white matter of the frontal and occipital regions obtained from four patients with parkinsonism-dementia (PD), eight with amyotrophic lateral sclerosis (ALS), and four neurologically normal controls from Guam. Zn content in gray matter from the frontal cortex in ALS and PD cases was significantly decreased, compared with that of controls (p < 0.05). No significant differences were found in the Zn content of white matter from the frontal cortex, and/or gray and white matter from the occipital cortex between the groups. The Zn content in gray matter from both frontal and occipital regions was less in ALS and PD patients than in controls. Fe content in gray matter from the frontal cortex of ALS and PD increased significantly compared with that of controls (p < 0.05). Fe content in white matter from the frontal cortex in PD patients was greater than in controls (p < 0.05), with an overall difference: controls < ALS < PD. These data indicate that an increase in Fe in gray and white matter, and a decrease concentration of Zn in gray matter, combined with an excess and deficiency of bioavailable aluminum and calcium, respectively, may be involved in the pathogenic process of these disorders. Authors Semchuk KM. Love EJ. Lee RG. Institution Department of Community Health Sciences, Faculty of Medicine, University of Calgary, Canada. Title Parkinson's disease: a test of the multifactorial etiologic hypothesis. Source Neurology. 43(6):1173-80, 1993 Jun. Abstract We studied the relative etiologic importance upon the development of Parkinson's disease (PD) of occupational exposure to herbicides and other compounds, ionizing radiation exposure, family history of PD and essential tremor, smoking, and history of various viral and other medical conditions. We identified patients (n = 130) with neurologist-confirmed idiopathic PD through contacts with Calgary general hospitals, long-term care facilities, neurologists, the Movement Disorder Clinic, and the Parkinson's Society of Southern Alberta, and selected two matched (by sex and age +/- 2.5 years) community controls for each case by random digit dialing. We obtained lifetime work, chemical, radiation, medical, and smoking exposure histories and family histories of PD and essential tremor by personal interviews, and analyzed the data using conditional logistic regression for matched sets. After controlling for potential confounding and interaction between the exposure variables, using multivariate statistical methods, having a family history of PD was the strongest predictor of PD risk, followed by head trauma and then occupational herbicide use. Cases and controls did not differ in their previous exposures to smoking or ionizing radiation; family history of essential tremor; work-related contact with aluminum, carbon monoxide, cyanide, manganese, mercury, or mineral oils; or history of arteriosclerosis, chicken pox, encephalitis, hypertension, hypotension, measles, mumps, rubella, or Spanish flu. These results support the hypothesis of a multifactorial etiology for PD, probably involving genetic, environmental, trauma, and possibly other factors. Authors Doering LC. Institution Division of Anatomy, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. Title Probing modifications of the neuronal cytoskeleton. [Review] Source Molecular Neurobiology. 7(3-4):265-91, 1993 Fall-Winter. Abstract The prominent death of central neurons in Alzheimer's and Parkinson's is reflected by changes in cell shape and by the formation of characteristic cytoskeletal inclusions (neurofibrillary tangles, Lewy bodies). This review focuses on the biology of neurofilaments and microtubule-associated proteins and identifies changes that can occur to these elements from basic and clinical research perspectives. Attention is directed at certain advances in neurobiology that have been especially integral to the identification of epitope domains, protein isoforms, and posttranslational (phosphorylation) events related to the composition, development, and structure of the common cytoskeletal modifications. Recently, a number of experimental strategies have emerged to simulate the aberrant changes in neurodegenerative disorders and gain insight into possible molecular events that contribute to alterations of the cytoskeleton. Descriptions of specific systems used to induce modifications are presented. In particular, unique neural transplantation methods in animals have been used to probe possible molecular and cellular conditions concerned with abnormal cytoskeletal changes in neurons. [References: 255] Authors Olanow CW. Institution Department of Neurology, Psychiatry and Pharmacology, University of South Florida, Tampa. Title A rationale for monoamine oxidase inhibition as neuroprotective therapy for Parkinson's disease. [Review] Source Movement Disorders. 8 Suppl 1:S1-7, 1993. Abstract Neurons in the substantia nigra may be vulnerable to oxidant stress because (a) the metabolism of dopamine generates peroxides, which, in the presence of iron, can lead to the formation of the highly reactive hydroxyl free radical; and (b) neuromelanin within nigral neurons can bind metals such as iron and aluminum and thereby promote the site-specific formation of free radicals. Postmortem studies show increased iron, decreased glutathione, and increased lipid peroxidation in the substantia nigra of patients with Parkinson's disease (PD). Recent studies also report iron and aluminum accumulation within neuromelanin granules of patients with PD. These findings suggest that the substantia nigra in the patient with PD is in a state of oxidant stress and that antioxidant therapy might protect residual dopamine neurons and slow the natural progression of PD. Selective inhibitors of monoamine oxidase type B (MAO-B) have been chosen for study because of their capacity to interfere with the oxidative metabolism of dopamine and so diminish the likelihood that free radicals will be formed. Initial studies demonstrate that the MAO-B inhibitor L-deprenyl (selegiline) delays the development of disability in otherwise untreated patients with early Parkinson's disease. Although the mechanism responsible for these observations remains unclear, these results are consistent with the possibility that L-deprenyl provides neuroprotective effects. [References: 46] Authors Good PF. Olanow CW. Perl DP. Institution Department of Pathology, Mt. Sinai Medical Center, New York, NY 10029. Title Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. Source Brain Research. 593(2):343-6, 1992 Oct 16. Abstract The Laser Microprobe Mass Analyzer (LAMMA) is a sensitive instrument for identifying and localizing trace elements in tissue samples. Using LAMMA, we have examined melanin-containing neurons of the substantia nigra in patients with Parkinson's disease (PD) and controls. We found that iron significantly accumulates within neuromelanin granules of patients with PD compared to controls. Increased aluminum was found in the neuromelanin granules of 2 of 3 PD cases but in no controls. The accumulation of iron and aluminum, which are known to promote oxidant stress, may account for the selective degeneration of neuromelanin-containing neurons in PD. Authors Exley C. Birchall JD. Institution Institute of Aquaculture, University of Stirling, Scotland, U.K. Title The cellular toxicity of aluminium. Source Journal of Theoretical Biology. 159(1):83-98, 1992 Nov 7. Abstract Aluminium is a serious environmental toxicant and is inimical to biota. Omnipresent, it is linked with a number of disorders in man including Alzheimer's disease, Parkinson's dementia and osteomalacia. Evidence supporting aluminium as an aetiological agent in such disorders is not conclusive and suffers principally from a lack of consensus with respect to aluminium's toxic mode of action. Obligatory to the elucidation of toxic mechanisms is an understanding of the biological availability of aluminium. This describes the fate of and response to aluminium in any biological system and is thus an important influence of the toxicity of aluminium. A general theme in much aluminium toxicity is an accelerated cell death. Herein mechanisms are described to account for cell death from both acute and chronic aluminium challenges. Aluminium associations with both extracellular surfaces and intracellular ligands are implicated. The cellular response to aluminium is found to be biphasic having both stimulatory and inhibitory components. In either case the disruption of second messenger systems is observed and GTPase cycles are potential target sites. Specific ligands for aluminium at these sites are unknown though are likely to be proteins upon which oxygen-based functional groups are orientated to give exceptionally strong binding with the free aluminium ion. Authors Halliwell B. Institution Division of Pulmonary-Critical Care Medicine, UC-Davis Medical Center, Sacramento 95817. Title Reactive oxygen species and the central nervous system. [Review] Source Journal of Neurochemistry. 59(5):1609-23, 1992 Nov. Abstract Radicals are species containing one or more unpaired electrons, such as nitric oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2.- and H2O2 can result in tissue damage, which often involves generation of highly reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron or copper ions. An important form of antioxidant defense is the storage and transport of iron and copper ions in forms that will not catalyze formation of reactive radicals. Tissue injury, e.g., by ischemia or trauma, can cause increased metal ion availability and accelerate free radical reactions. This may be especially important in the brain because areas of this organ are rich in iron and CSF cannot bind released iron ions. Oxidative stress on nervous tissue can produce damage by several interacting mechanisms, including increases in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that free radical reactions are involved in the neurotoxicity of aluminum and in damage to the substantia nigra in patients with Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain-breaking antioxidants. Careful precautions must be used in the design of antioxidants for therapeutic use. [References: 183] Authors Yasui M. Kihira T. Ota K. Institution Division of Neurological Diseases, Wakayama Medical College, Japan. Title Calcium, magnesium and aluminum concentrations in Parkinson's disease. Source Neurotoxicology. 13(3):593-600, 1992 Fall. Abstract Concentrations of calcium (Ca) and aluminum (Al) were measured by neutron activation analysis and that of magnesium (Mg) by inductively coupled plasma emission spectrometry in 26 regions of Parkinson's disease (PD) and control brains. Ca concentration was unchanged in all anatomic subregions of PD brains compared with control brains. Mg concentration was lower in cortex, white matter, basal ganglia and brain stem of PD brains compared to control brains (p < 0.01). Al concentration in the substantia nigra, caudate nucleus and globus pallidus was higher in PD brains compared to controls (p < 0.05) and significantly higher in gray matter and the basal ganglia (p < 0.01). These studies are consistent with other observations linking high concentrations of Al and low levels of Mg in the pathogenesis of CNS degeneration and PD. Authors Perl DP. Good PF. Institution Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029. Title Aluminium and the neurofibrillary tangle: results of tissue microprobe studies. [Review] Source Ciba Foundation Symposium. 169:217-27; discussion 227-36, 1992. Abstract Despite the contradictory results of studies attempting to compare the bulk brain tissue aluminium content of specimens from Alzheimer's disease patients and controls, microprobe studies from our laboratory have consistently documented evidence of selective accumulation of the element within the neurofibrillary tangle-bearing cells associated with this condition. Laser microprobe mass analysis (a highly sensitive and precise technique for trace elemental microprobe analysis) has now demonstrated that the most prominent aluminium accumulations occur within the neurofibrillary tangle itself. Similar findings have been obtained from microprobe studies of the neurofibrillary tangles which are a characteristic feature of amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. Although the intraneuronal localization of aluminium in the Guam-derived specimens is similar to that of Alzheimer's disease, the concentration of aluminium is considerably higher than is encountered in Alzheimer's disease specimens. We conclude that aluminium is an integral component of the neurofibrillary tangle and raise the possibility that the cross-linking properties of this highly reactive metal may stabilize the constituent cytoskeletal proteins which make up this pathological structure. [References: 37] Authors Wisniewski HM. Wen GY. Institution New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314. Title Aluminium and Alzheimer's disease. [Review] Source Ciba Foundation Symposium. 169:142-54; discussion 154-64, 1992. Abstract The hypothesis that aluminium (Al) is a cause of (or a risk factor in) the development of beta-amyloid plaques and neurofibrillary tangles (NFT) and dementia in Alzheimer's disease (AD) is based on studies by Wisniewski et al, Klatzo et al and Terry & Pena in 1965 that showed that injection of experimental animals with Al compounds induces the formation of NFT. Other publications revealed that Al affects cognitive functions in experimental animals and humans undergoing dialysis for renal failure. Electron probe and laser microprobe mass analysis (LAMMA) studies have demonstrated the presence of Al in NFT and cores of amyloid stars and nuclei of neurons in AD patients. Other studies have indicated the association between amyotrophic lateral sclerosis/Guam parkinsonism-dementia complex and Al in the environment. A recent report suggests that the chelating agent desferrioxamine slows the rate of cognitive decline in AD patients. Extensive studies of the pathology of AD and Al-induced encephalopathy by our group and others indicate that Al does not cause Alzheimer's disease neuropathology. However, under certain conditions, cognition can be affected when Al enters the brain. Therefore, for individuals with renal failure or undergoing dialysis or individuals with a damaged blood-brain barrier, the intake of Al should be controlled. [References: 46] Authors Yasui M. Kihira T. Ota K. Mukoyama M. Adachi K. Institution Division of Neurological Diseases, Wakayama Medical College. Title [Aluminum deposition in the central nervous system tissues of patients with Parkinson's disease]. [Japanese] Source Rinsho Shinkeigaku - Clinical Neurology. 31(10):1095-8, 1991 Oct. Abstract Aluminum (Al) concentration in the 26 anatomic central nervous system (CNS) regions, liver, kidney, spleen and heart of our patients with Parkinson's disease, and five neurologically normal controls was measured by a non-destructive neutron activation analysis (NAA), in order to clarify the implication of Al on pathogenesis of Parkinson's disease. Al concentration in substantia nigra, caudate nucleus and globus pallidus increased in patients with Parkinson's disease more than that in controls (p less than 0.05). There was a significant difference in Al concentration of gray matter and basal ganglia in Parkinson's disease, compared with those of controls (p less than 0.01). It is likely that high Al deposition in pathological foci responsible for Parkinson's disease might be implicated in the pathogenesis of Parkinson's disease. Authors Kiss SA. Dombovari J. Oncsik M. Institution Borsod Chemical Works, Kazincbarcika, Hungary. Title Magnesium inhibits the harmful effects on plants of some toxic elements. Source Magnesium Research. 4(1):3-7, 1991 Mar. Abstract Cadmium and aluminium ions - especially in acid soils - are taken up by plants which then become poisoned by them. As a result the roots of the plants become deformed, and the green parts become chlorotic and underdeveloped. The yield will thus be sharply reduced. Culture fluid and culture pot experiments have shown that the toxic effects can be inhibited by magnesium. Investigations have proved that the inhibition is competitive and is based on the antagonism of cadmium and aluminium towards magnesium. Toxic cadmium and aluminium concentrations in the soil can be decreased by the use of non-acidifying fertilizers, and inhibited or prevented with fertilizers containing magnesium, eg Agronit (28% N and 2.5% Mg) or Kardonit (28% N and 5.5% Mg) (Borsod Chemical Works). Cadmium and aluminium taken up by plants are equally detrimental to animal and human organisms through the nutrition chain. For example cadmium may cause sterility, while aluminium may be implicated in Alzheimer's and Parkinson's disease. Magnesium moderates the effects of these two toxic elements in the human organism as well as in plants. Authors Hirsch EC. Brandel JP. Galle P. Javoy-Agid F. Agid Y. Institution INSERM U289, Hopital de la Salpetriere, Paris, France. Title Iron and aluminum increase in the substantia nigra of patients with Parkinson's disease: an X-ray microanalysis. Source Journal of Neurochemistry. 56(2):446-51, 1991 Feb. Abstract The levels of different elements were studied by x-ray microanalysis in the substantia nigra and the central gray substance of patients with Parkinson's disease, progressive supranuclear palsy, and matched controls. In control brains, only iron, potassium, silicum, sodium, sulfur, and zinc were within the limit of detection of the technique. The abundance of each element was different, but their respective concentrations in the two brain regions were similar, except for sulfur levels which were higher on neuromelanin aggregates in the substantia nigra than in nigral regions lacking neuromelanin, and in the central gray substance. In Parkinson's disease, but not in progressive supranuclear palsy, nigral iron levels increased in regions devoid of neuromelanin and decreased on neuromelanin aggregates, but were unchanged in the central gray substance, when compared to control values. Concentrations of the other elements in the central gray substance and substantia nigra were not different from controls in brains from patients with Parkinson's disease and progressive supranuclear palsy. Analysis of Lewy bodies in the parkinsonian substantia nigra revealed high levels of iron and the presence of aluminum. Metal abundance was not affected in progressive supranuclear palsy, in spite of the nigral cell death. This suggests that the increased iron levels and the detection of aluminum observed in Parkinson's disease are not solely the consequence of the neuronal degeneration. Authors Garruto RM. Institution Laboratory of Central Nervous System Studies, National Institutes of Health, Bethesda, Maryland 20892. Title Pacific paradigms of environmentally-induced neurological disorders: clinical, epidemiological and molecular perspectives. [Review] Source Neurotoxicology. 12(3):347-77, 1991 Fall. Abstract During the past quarter century biomedical scientists have begun to recognize the unique opportunities for studying disease etiology and mechanisms of pathogenesis in non-Western anthropological populations with focal, endemic diseases. Such natural experiments as they are called, are important paradigms for solving etiological and epidemiological problems of widespread medical significance, with an ultimate goal towards treatment and prevention. The systematic search for etiological factors and mechanisms of pathogenesis of neurodegenerative disorders is perhaps nowhere better exemplified than in the western Pacific. During the past three decades, the opportunistic and multidisciplinary study of hyperendemic foci of amyotrophic lateral sclerosis and parkinsonism-dementia which occur in different cultures, in different ecological zones and among genetically divergent populations have served as natural models that have had a major impact on our thinking and enhanced our understanding of these and other neurodegenerative disorders such as Alzheimer disease and the process of early neuronal aging. Our cross-disciplinary approach to these intriguing neurobiological problems and the accumulated epidemiological, genetic, cellular and molecular evidence strongly implicates environmental factors in their causation, specifically the role of aluminum and its interaction with calcium in neuronal degeneration. As a direct consequence of our studies in these Pacific populations, we have undertaken the long-term development of experimental models of neuronal degeneration, in an attempt to understand the cellular and molecular mechanisms by which these toxicants affect the central nervous system. Our experimental studies have resulted in the establishment of an aluminum-induced chronic myelopathy in rabbits and the development of neurofilamentous lesions after low-dose aluminum administration in cell culture. These studies clearly demonstrate the philosophy that chronic rather than acute experimental models of toxicity are necessary in order to enhance our understanding of human neurodegenerative disorders with long-latency and slow progression. Finally, the ultimate significance of these Pacific paradigms may well depend on our ability to comprehensively evaluate and synthesize the growing body of relevant scientific data from other human disorders and from widely divergent academic fields, as well as our ability to recognize emerging new models in nature. [References: 211] Authors Wechsler LS. Checkoway H. Franklin GM. Costa LG. Institution Department of Environmental Health, University of Washington, Seattle 98195. Title A pilot study of occupational and environmental risk factors for Parkinson's disease. Source Neurotoxicology. 12(3):387-92, 1991 Fall. Abstract Increasingly, the etiology of Parkinson's disease (PD) has been linked to exposures to environmental toxicants. This epidemiologic pilot study used a self-administered questionnaire among 34 PD cases and 22 other neurology clinic control patients. All subjects were at least 40 years old. Risk factors investigated included occupation, well-water use, pesticide use, metal exposures, medical history, smoking, alcohol consumption, and drug use. Twenty-six percent of the male PD cases reported having been employed in farming versus eleven percent for male controls (OR = 3.1, 95% C.I. = 0.3 to 35). Sixteen percent of male cases versus none of the controls reported employment as welders. No clear trends involving exposure to either occupational or home pesticides emerged. In assessing occupational exposures to metals, aluminum and copper exposures tended to be more common among male cases than male controls. Additionally, as reported in other studies, smoking showed an inverse relationship with PD. Although the findings reported here are provocative, these results are statistically imprecise and must be interpreted cautiously because of the small number of subjects included in the study. Authors Perl DP. Good PF. Institution Department of Pathology, Arthur M. Fishberg Center for Neurobiology, Mount Sinai Medical Center, New York, New York 10029. Title Aluminum, Alzheimer's disease, and the olfactory system. [Review] Source Annals of the New York Academy of Sciences. 640:8-13, 1991. Abstract In Alzheimer's disease, it has been recognized that there is a dramatic tendency for the development of neurofibrillary tangles among neurons of cortical regions associated with the olfactory system. We have demonstrated that neurofibrillary tangle-bearing neurons contain dramatically elevated levels of aluminum. The olfactory system, the only portion of the central nervous system with exposure to the external environment, is uniquely capable of uptake and transneuronal spread of exogenous substances. We argue that inasmuch as aluminum is not employed in any physiologic process, these deposits must arise from exogenous sources. Using parkinsonism-dementia complex of Guam as a model, we present data which suggest that the olfactory system is particularly vulnerable to damage and is affected very early in the disease. This supports the concept that etiologic agents of importance to this epidemic may be airborne in nature and may enter the central nervous system via the olfactory pathways. [References: 24] Authors Youdim MB. Ben-Shachar D. Riederer P. Institution Technion-Faculty of Medicine, Rappaport Family Research Institute, Haifa, Israel. Title Iron in brain function and dysfunction with emphasis on Parkinson's disease. [Review] Source European Neurology. 31 Suppl 1:34-40, 1991. Abstract Metals such as lead, zinc, copper, aluminum and manganese have been implicated in neuropsychiatric disorders. However, until fairly recently the role of iron in brain function was rather obscure, because little attention was paid to its metabolism in the brain. It is now apparent that maintenance of brain iron homoeostasis is important for the normal functioning of his organ. Most of the studies have been directed towards the cognitive and attentional deficit resulting from nutritional iron deficiency. Evidence so far suggests subsensitivity of striatal dopamine neurotransmission. By contrast the selective increase in free iron in the substantia nigra pars compacta of parkinsonian brains is thought to initiate oxidative stress, from iron-induced liberation of cytotoxic oxygen free radicals. Such radicals are known to promote membrane fluidity, alteration in cellular calcium homoeostasis, lipid peroxidation and finally cell death in systemic organs. Evidence supporting similar processes being responsible for nigrostriatal dopamine neuron degeneration in Parkinson's disease is now becoming available. Such possibilities afford the development of neuroprotective drugs as a means to retard the progression of this disorder. These include other selective monoamine oxidase B inhibitors, iron chelators with the ability to cross the blood-brain barrier, selective calcium channel antagonists and mitochondrial electron transport system protectors. [References: 45] John Cottingham [log in to unmask] OR [log in to unmask]