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PubMed2000

Monoclonal antibodies against Epstein-Barr virus cross-react with alpha-synuclein in human brain.

Using antibodies generated against the latent membrane protein 1 of Epstein-Barr virus, intense immunoreactivity of Lewy bodies (in PD and dementia with Lewy bodies) and glial cytoplasmic inclusions (in multiple system atrophy) was demonstrated. ELISA and Western blotting techniques confirmed that this immunolabeling was due to cross-reactivity of the antiviral antibody with alpha-synuclein, a neuronal protein implicated in the pathogenesis of PD. This example of cross-reactivity between Epstein-Barr virus and alpha-synuclein may bear implications for further elucidating infectious or autoimmune mechanisms in PD.

Antibodies, Monoclonal↗

PubMed2005

Neurodegenerative diseases: an overview of environmental risk factors.

The population of the United States is aging, and an ever-increasing number of Americans are afflicted with neurodegenerative diseases. Because the pathogenesis of many of these diseases remains unknown, we must consider that environmental factors may play a causal role. This review provides an overview of the epidemiologic evidence for environmental etiologies for neurodegenerative diseases such as Alzheimer disease, Parkinson disease, parkinsonian syndromes (multiple system atrophy and progressive supranuclear palsy), and amyotrophic lateral sclerosis. Epidemiologic evidence for an association between environmental agents' exposure and neurodegenerative diseases is not conclusive. However, there are indications that there may be causal links, and the need for more research is obvious.

Age Factors↗

PubMed2002

Identification of parkinsonism and Parkinson's disease.

Parkinson's disease is a common movement disorder associated with considerable disability. The clinical syndrome of parkinsonism is based on the presence of core clinical features of rest tremor, bradykinesia, rigidity and impaired postural reflexes or gait. Parkinsonism is most often caused by Parkinson's disease, but can also be caused by other disorders, including cerebrovascular disease, multiple-system atrophy, progressive supranuclear palsy and other disorders. Parkinsonism can be identified by questionnaires and confirmed in person or by videotaped clinical examinations. The identification of presymptomatic cases remains problematic but is motivated by the hope for treatment before symptoms appear. Quantitative approaches to the diagnosis of parkinsonism based on the measurement of the cardinal features are available. Clinical approaches should include identification of features atypical for Parkinson's disease, which exclude the diagnosis, and documentation of a response to dopaminergic medications, which support a diagnosis of Parkinson's disease. Loss of smell and visual dysfunction are found in early patients and may be useful in screening protocols. In addition, behavioral changes, including depressive symptoms, may be detected in presymptomatic cases. Cognitive changes, such as impaired set shifting, have been observed in early Parkinson's disease, but can be seen with other causes of parkinsonism. Neuroimaging techniques, including positron emission tomography or single-photon emission computed tomography, are available to quantify dopaminergic neurons, while magnetic resonance imaging may be helpful in differentiating other forms of parkinsonism from Parkinson's disease. There are numerous approaches available to the identification of parkinsonism and Parkinson's disease. The gold standard remains a clinical diagnosis, confirmed by autopsy.

Humans↗

PubMed1994

[A case of Shy-Drager syndrome complicated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and incomplete paralysis of bilateral vocal cords].

A 67-year-old man with SIADH complicated by slowly progressing autonomic failure was described. The patient noticed constipation at the age of 57. In the following years, he suffered from urinary incontinence, depletion of sweating, impotence, sleeplessness with snore, and dizziness while walking. Physical examination revealed a masked oily face with slight cerebellar disturbance. Abnormality of autonomic function tests was recognized and he was diagnosed as Shy-Drager syndrome with gradually progressing, diffuse autonomic failure accompanied by slight cerebellar ataxia and Parkinsonism. Both serum sodium level and plasma osmotic pressure were reduced, whereas daily sodium excretion was more than 100mEq and urinary osmolality was about 500mOsm/kgH2O. His renal function was intact, and the adrenocortical and thyroid hormone levels were normal, then criteria of SIADH was fulfilled. SIADH was thought to have occurred on the basis of Shy-Drager syndrome. Water load test showed failure of adequate water diuresis, but intravenous phenytoin administration following the water load test ameliorated the diuresis to normal. The relationship between plasma osmolality and the ADH response indicates that ADH was adequately secreted in response to the increase in plasma osmolality but not suppressed in response to the decrease in plasma osmolality below 280mOsm/kgH2O. These results suggest that ADH synthesis in the hypothalamus and its secretion from the pituitary gland were both intact. The response of ADH secretion to the orthostatic hypotension induced by head-up tilt was quite blunted, being compatible with Shy-Drager Syndrome. Sleep disturbance was studied by polysomnography and laryngoscopy, and was revealed to be based upon severe sleep apnea due to incomplete paralysis of the bilateral vocal cords. Sleep apnea due to vocal cord paralysis is sometimes found to be complicated in patients with multiple system atrophy (MSA) including Shy-Drager syndrome, and is known as Gerhardt syndrome. This is the first report on a case of Shy-Drager syndrome complicated with SIADH and bilateral vocal cord paralysis. In this case, SIADH is caused by impaired afferent pathways from baroreceptors to the hypothalamus, which transfer inhibitory stimuli on ADH secretion. It is suggested that Shy-Drager syndrome should be considered one of the causes of SIADH.

Aged↗

PubMed2001

Parkinson's disease and other alpha-synucleinopathies.

Parkinson's disease is the most common movement disorder and the second most common neurodegenerative disease. Neuropathologically, it is characterized by the degeneration of nerve cells that develop filamentous inclusions in the form of Lewy bodies and Lewy neurites. Recent work has shown that rare, familial forms of Parkinson's disease are caused by missense mutations in the alpha-synuclein gene and that the filamentous lesions of Parkinson's disease are made of alpha-synuclein. The same is true of the Lewy body pathology that is associated with other neurodegenerative diseases, such as dementia with Lewy bodies. The filamentous inclusions of multiple system atrophy have also been found to be made of alpha-synuclein, thus providing an unexpected molecular link with Lewy body diseases. Recombinant alpha-synuclein assembles into filaments with similar morphologies to those found in the human diseases and with a cross-beta diffraction pattern characteristic of amyloid. The related proteins beta-synuclein and gamma-synuclein are poor at assembling into filaments. They are not present in the pathological filamentous lesions and have not been found to be linked to genetic disease. The new work has established the alpha-synucleinopathies as a major class of neurodegenerative disease.

Animals↗

PubMed1998

Etiology of parkinsonism in a Brazilian movement disorders clinic.

OBJECTIVE: The aim of the present study is to investigate whether there are geographic differences in the etiology of parkinsonism (PA). BACKGROUND: 72% of patients with PA evaluated at movement disorders clinics in the Northern Hemisphere are diagnosed with Parkinson's disease (PD). Data regarding other regions are not available. METHODS: We reviewed the charts of all patients with PA seen at the Federal University of Minas Gerais Movement Disorders Clinic from July 1993 through October 1995. PA was diagnosed by the presence of at least two of the following: rest tremor, bradykinesia, rigidity, and postural instability. The different etiologies were diagnosed based on standard clinical criteria. RESULTS: During the period of the study, PA was recognized in 338 subjects. The following clinical diagnoses were made: PD (68.9%), drug-induced PA (DIP) (13.3%), vascular PA (4.7%), Progressive supranuclear palsy (PSP) (2%), multiple system atrophy (MSA) (1.8%), others (9.7%). Cinnarizine, haloperidol and flunarizine were the commonest drugs related to DIP. CONCLUSIONS: Similarly to other studies, PD accounts for about 70% of PA patients. However, there are differences between our results and previous series. DIP is much more common in the present series. This may be accounted for a more liberal use of antidopaminergic drugs in our environment, especially Calcium channel blockers. The lower frequency of MSA and PSP in our study may reflect a short follow-up, since many patients initially diagnosed with PD later are found to have Parkinson-plus syndromes.

Aged↗

PubMed2000

Early Parkinson's disease: what is the best approach to treatment.

Early and correct diagnosis and treatment of Parkinson's disease (PD) are crucial for the patient's well being. At the first visit, it is important to deal with the patient's misconceptions of the disease and its course, to offer sources of information and to suggest exercises. To make a correct initial diagnosis of PD we need to assess the course of the initial levodopa responsiveness. The most frequent challenges in diagnosing PD are the conditions of essential tremor and multiple system atrophy. PD has 3 stages of development: (i) early--from the onset of symptoms to the appearance of motor fluctuations; (ii) middle--from motor fluctuations to the appearance of moderate-to-severe disability; and (iii) advanced--when moderate-to-severe disability is present. The medical treatment of early PD should be started when functional disability appears, which is a different threshold for each patient. For patients below 65 years old, or above 65 years old but with preserved mental function and with no severe comorbidity, initial monotherapy with a dopamine agonist is advisable. This approach appears to delay the appearance and reduce the amount of late motor complications with subsequent levodopa treatment. All dopamine agonists have similar efficacy, which is less than that of levodopa. It is important to consider the adverse effect profile when a choice for initial or adjunctive therapy is made. When levodopa therapy is started as an adjunct in younger patients or as initial monotherapy in older patients, sustained-release levodopa preparations are preferred. They have a longer half-life and possibly stimulate the dopamine receptors more continuously. Anticholinergic drugs are appropriate for younger patients with tremor-dominant PD. Amantadine is mainly used for dyskinesia control. Catechol-O-methyl-transferase inhibitors and neurosurgery are not treatments of choice for early PD but can be very effective for more advanced disease. The presence of presymptomatic markers of PD, such as changes in odour detection, handwriting, speech, movement time of self-initiated motor acts, personality traits, presence of antibodies against dopaminergic neurons, pattern of positron emission tomography results, appearance of mitochondrial DNA mutation profiles, etc., appear to be very important in the light of the emerging neuroprotective therapies. Neuroprotection is aimed at slowing the rate of disease progression. Selegiline has been shown to cause a mild delay in the need for levodopa, possibly suggesting some protection. However, this initial benefit was not sustained in long term studies. Currently, there is no neuroprotective drug for PD.

Animals↗

PubMed2001

Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management.

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson's disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson's disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson's disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson's disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson's disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson's disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, alpha1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.

Blood Volume↗

PubMed2006

Gluten sensitivity in Japanese patients with adult-onset cerebellar ataxia.

OBJECTIVE: Gluten sensitivity is associated with multiple neurological abnormalities including gluten ataxia, motor neuron disease-like neuropathy, small fiber type neuropathy, cognitive impairment, and even parkinsonism. We investigated whether or not gluten sensitivity is involved in Japanese patients with idiopathic cerebellar ataxia with extracerebellar presentation. PATIENTS OR MATERIALS: Fourteen patients with idiopathic cerebellar ataxia with extracerebellar presentation (autonomic instability, parkinsonism, or pyramidal dysfunction in varying combinations) were screened for anti-gliadin antibodies (AGA) to analyze for the presence or absence of gluten sensitivity. Patients with typical MR findings of multiple system atrophy of the cerebellar type were excluded. As disease controls without cerebellar ataxia, 9 patients with Parkinson's disease and 18 patients with amyotrophic lateral sclerosis were screened for AGA. Forty-seven normal controls were also screened for AGA. RESULTS: We found a high prevalence of AGA in 5 (36%) of 14 cerebellar ataxia patients, but in only 1 (4%) of 27 disease controls without cerebellar ataxia (odds ratio, 14.4; 95% CI, 1.41147; p<0.05) and in only 1 (2%) of 47 normal controls (odds ratio, 25.6; 95% CI, 2.66246; p<0.001). Among the cerebellar ataxia patients, atypical features such as sensorimotor neuropathy and/or mild cognitive impairment were more prevalent in the AGA-positive group (60%) than in the AGA-negative group (0%). In one of the ataxic patients with AGA, a gluten-free diet had positive effects on neurological symptoms and nutritional status. CONCLUSION: Gluten sensitivity is involved in at least some of the unexplained neurological symptoms of Japanese patients with adult-onset, sporadic cerebellar ataxia.

Age of Onset↗

PubMed2004

Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration.

Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein fibrils characterize many different neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, Huntington's disease, and the transmissible 'prion' dementias. There is strong evidence from genetic, transgenic mouse and biochemical studies to support the idea that the accumulation of protein aggregates in the brain plays a seminal role in the pathogenesis of these diseases. How monomeric proteins ultimately convert to highly polymeric deposits is unknown. However, studies employing, synthetic, cell-derived and purified recombinant proteins suggest that amyloid proteins first come together to form soluble low n-oligomers. Further association of these oligomers results in higher molecular weight assemblies including so-called 'protofibrils' and 'ADDLs' and these eventually exceed solubility limits until, finally, they are deposited as amyloid fibrils. With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction.

Alzheimer Disease↗

PubMed2004

Morning glory sign: a particular MR finding in progressive supranuclear palsy.

BACKGROUND AND PURPOSE: We have encountered a peculiar atrophic change in the midbrain in some patients with parkinsonian syndromes. We discovered these patients had vertical supranuclear gaze-palsy, an eye movement disorder. The purpose of this study was to elucidate whether this atrophic pattern of the midbrain (which we have termed morning glory sign) is related to the vertical eye movement disorder, in particular to progressive supranuclear palsy (PSP). METHODS: We reviewed T2-weighted axial images obtained from 42 patients with parkinsonian syndromes, including five patients with PSP, 23 patients with Parkinson's disease, and 14 patients with multiple system atrophy (MSA). We focused on a specific atrophy of the midbrain, the morning glory sign, which is a concavity of the lateral margin of the tegmentum of the midbrain. RESULTS: The morning glory sign was detected in four of the five patients with PSP and in one (striatonigral degeneration; SND) of the14 patients with MSA. All morning glory sign patients had vertical supranuclear gaze-palsy, as did the one PSP patient without the morning glory sign. Vertical supranuclear gaze-palsy was seen in no other patients (23 patients with Parkinson's disease and 13 patients with MSA) who lacked the morning glory sign. CONCLUSIONS: Morphologically, the morning glory sign is believed to be related to vertical supranuclear gaze-palsy. This sign should be considered a useful clue when diagnosing PSP.

Aged↗

PubMed1991

[Diagnosis and treatment of Parkinson's disease in the elderly].

The 159 patients with Parkinson's disease with onset after the age of 50 (mean: 62.3 years) were studied with reference to diagnosis and treatment. The results were as follows: 1. Other than the characteristic features, the symptoms at onset were depression (6% of the patients), lumbago (4%), hemiplegia-like (4%) and dizziness (3%), causing misdiagnoses in some of the patients. Among 159 patients studied, the severity most frequent was Yahr stage 3 (63%) at first examination, indicating the necessity of earlier diagnosis. 2. Magnetic resonance imaging (MRI) of the substantia nigra and striatum was investigated using a 1.5 Tesla field and T2-weighted images, which gave no specific results concerning diagnosis and severity. However, it was useful in differential diagnosis between this disease and parkinsonism caused by multiple system atrophy and cerebrovascular diseases. 3. With 123I-IMP SPECT, decrease in blood flow in the frontal and temporal lobes correlated with the severity (Yahr stage) of the disease. Regarding cognitive functions the scores of Hasegawa's Dementia Scale and Mini-Mental State showed a highly significant correlation with the amount of blood flow in frontal and parietal lobes, suggesting that dementia might be caused by dysfunction of these lobes. 4. In 98 patients treated with levodopa mixed with dopa-economizers for more than a year, the maximum improvement was small in severely disabled patients of Yahr stage 5 and 4 because none improved to stage 3A or below (3A is an arbitrary criterion meaning mild involvement in stage 3 with 3P meaning more severe cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

[An autopsy case of progressive supranuclear palsy with central pontine myelinolysis].

An autopsy case of progressive supranuclear palsy (PSP) associated with central pontine myelinolysis (CPM) is reported. A 73-year-old male patient suffered from gait disturbance for about 5 years. The clinical features were characterized by gradual development of supranuclear ophthalmoplegia, tremor, bradykinesia, rigidity, neck dystonia, dementia and pseudobulbar palsy at the advanced stage of his illness. Treatment with levodopa did not improve his neurological signs and symptoms. PSP or multiple system atrophy was considered as a clinical diagnosis of the patient. He died of pneumonia, acute pancreatitis and liver dysfunction in November 1985. The main neuropathological findings were neuronal loss and gliosis with neurofibrillary tangles of globose type in the globus pallidus, subthalamic nucleus, substantia nigra and dentate nucleus, and at the base of the pons, bilateral and symmetrical demyelination was found. In addition, myelin staining revealed circumscribed pallor in the cerebral white matter. The histologic diagnosis was PSP associated with CPM. An association of PSP with CPM is rare in the elderly and possible etiologic factors of both diseases were discussed.

Aged↗

PubMed1996

[A case of idiopathic orthostatic hypotension manifesting sick sinus syndrome due to sympathetic nervous dysfunction].

A 67-year-old woman with idiopathic orthostatic hypotension was presented. The patient started to experience faintness on standing since 1993. During a physical examination, her systolic blood pressure fell from 148 to 50 mmHg on standing. Blood pressure responses to the mental arithmetic test and hyperventilation stress were normal. However, cold pressor test failed to increase blood pressure. These observations, with the finding that phase IV response on Valsalva's maneuver was absent, indicate afferent sympathetic nervous dysfunction. Peripheral neuropathy including diabetes mellitus and involvement of central nervous system such as multiple system atrophy were excluded. Holter ECG examination revealed a 3.9 second sinus arrest and bradycardia (total beats 88901/day). the blunted responses of the heart rate to atropine as well as isoproterenol further suggested the presence of sick sinus syndrome. Amezinium administration significantly improved her orthostatic hypotension and eliminated sinus arrest. These findings indicate that sympathetic nervous dysfunction could account for at least a part of the sick sinus syndrome in this patient.

Aged↗

PubMed2004

[Diseases other than Parkinson's disease presenting with parkinsonism].

Among the diseases causing parkinsonism, drug-induced parkinsonism is important because physicians often use anti-dopaminergic drugs such as benzamides for gastrointestinal disorders. In 28 patients with drug-induced parkinsonism, 13 (47%) showed persistent parkinsonism even 6 months after the cessation of the causative drugs. This means anti-dopaminergic drugs may bring subclinical parkinsonism to the clinical level especially in the elderly. Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy including striatonigral degeneration were recognized in 2003 as specific diseases by the National Health Insurance of Japan. The diagnostic criteria of PSP (the modification of NINDS-SPSP criteria) made by the study group of the Ministry of Health, Welfare and Labour (MHWL) of Japan has demonstrated that their sensitivity was 83% and specificity 97% in "probable PSP". Patients with CBD were surveyed among the main neurologic institutions in Japan using the provisional diagnostic criteria There were 151 patients with "probable CBD" and 13 with "definite CBD". Based on these data, the number of patients with PSP and CBD in 2001 was estimated as 6,400 (5.03 per 100,000) and 2,500 (1.93 per 100,000), respectively, in Japan. Neuroprotective drugs hold hope for the treatment of neurodegenerative diseases. Although many agents were reported to be neuroprotective for Parkinson's disease from in vitro studies, pramipexole, a dopamine agonist, is the only one with good clinical evidence based on neuroimaging. Other dopamine agonists as well as various nerve trophic factors may also have the same effects, though further confirmatory studies are necessary.

Female↗

PubMed2006

Unilateral Holmes tremor, clearly responsive to cerebrospinal fluid release, in a patient with an ischemic midbrain lesion and associated chronic hydrocephalic ventricle enlargement. Case report.

The authors describe a 58-year-old man with sudden onset of a unilateral tremor caused by a midbrain lesion that affected the substantia nigra and the cerebellothalamic pathway. There were also clinical and neuroimaging signs of a communicating chronic hydrocephalus. The patient was severely handicapped by this tremor, which was a typical Holmes tremor with rest, posture, and intention components. Parkinson disease or multiple-system atrophy as causes for the tremor could be ruled out by DaTSCAN and 123I iodobenzamide and single-photon emission computerized tomography (SPECT), respectively. The tremor was completely supressed by temporary and permanent cerebrospinal fluid release after ventriculoperitoneal shunt placement, without any additional medication, for a period of 6 months. Afterward, the tremor returned, and the patient had to be treated by a stereotactic electrode implantation in the contralateral ventralis intermedius nucleus, which led to complete tremor suppression during the 1.5-year follow-up period. In this case report, the authors present the clinical description and the electrophysiological, SPECT, and magnetic resonance imaging data of a rare combination of symptoms and their surgical treatment.

Brain Ischemia↗

PubMed1999

Brain Accumulation of Amyloid-beta in Non-Alzheimer Neurodegeneration.

We report an unusual case of amyotrophic lateral sclerosis (ALS) marked by extensive cerebral amyloid-beta deposition in small and medium-size vessels, capillaries, and perivascular plaques in the cerebral cortex, and in most leptomeningeal vessels. Despite considerable cerebral amyloidosis, the patient remained cognitively intact until death. For comparison with other neuro-degenerative diseases and normal aging, we assessed the densities of amyloid-beta-immunoreactive cortical vessels and plaques in matched frontal and temporal lobe sections from archival uncomplicated cases of Alzheimer's disease (N=10), Pick's disease (PkD; N=4), Parkinson's disease (PD; N=6), Diffuse Lewy body disease (DLBD; N=7), progressive supranuclear palsy (PSP; N=5), multiple systems atrophy (MSA; N=4), ALS (N=7), or normal aging (N=10) by semi-quantitative grading (0 to 3+). Moderate (2+) or abundant (3+) cerebrovascular amyloid-beta immunoreactivity was detected in 8/10 AD, 3/7 DLBD, 3/6 PD, 1 each with PSP or PkD, and 2/10 controls. Moderate or abundant densities of amyloid-beta-immunoreactive diffuse plaques were detected in all cases of AD or DLBD, 4/6 with PD, 3/5 with PSP, and 2/10 controls. Moderate or abundant amyloid-beta-immunoreactive mature (dense core) plaques were present in all cases of AD or DLBD, and 3 each with PD or PSP. Importantly, amyloid-beta-immunoreactivity was not observed in the 4 MSA or 7 archival ALS cases. This study demonstrates that prominent amyloid-beta accumulation in cerebral vessels and plaques occurs frequently in AD, DLBD, PSP, and PD, but not in ALS or MSA, indicating that the case described is unique. The lack of cognitive impairment in the case presented argues against the idea that extensive amyloid-beta deposition in the brain causes dementia.

Journal Article↗

PubMed2003

Alpha-synuclein aggregation and neurodegenerative diseases.

Alpha-synuclein is a neuronal protein originally identified in Alzheimer's disease (AD) amyloid plaques in 1993 and named non-Abeta component precursor (NACP) [92]. Later, the discovery of two missense mutations (G88C and G209A), which resulted in Ala30Pro (A30P) and Ala53Thr (A53T) substitutions, of the alpha-synuclein gene in certain autosomal-dominant early onset familial Parkinson's disease (PD) has greatly promoted the understanding of the role of alpha-synuclein in the pathogenesis of neurodegenerative diseases, such as PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) [5,6,51,75]. At present, it is widely accepted that alpha-synuclein may play a central role in several neurodegenerative disorders because of the presence of insoluble alpha-synuclein as the major fibrillar component of inclusion bodies. From the cloning of the human alpha-synuclein cDNA in 1993 to the present, alpha-synuclein has been carefully documented in many aspects. In this article, we review the progress of studies on alpha-synuclein and its role in alpha-synuclein-related neurodegenerative diseases.

Animals↗