The human NACP/α-synuclein gene: chromosome assignment to 4q21.3–q22 and TaqI RFLP analysis

Chen, Xiaohua; Silva, H.A.Rohan de; Pettenati, Mark J.; Rao, P. Nagesh; George-Hyslop, Peter St; Roses, Allen D.; Xia, Yu; Horsburgh, Karen; Uéda, Kenji; Saitoh, Tsunao

doi:10.1016/0888-7543(95)80237-g

Cited by 115 publications

(55 citation statements)

References 9 publications

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“…The human ␣ synuclein gene was previously mapped in the 4q21-q22 region (5). Genotype analysis in the Italian PD kindred with additional genetic markers showed recombination events.…”

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confidence: 99%

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

Polymeropoulos

Lavedan

Leroy

et al. 1997

Science

7,516

5,036

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Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.

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“…The human ␣ synuclein gene was previously mapped in the 4q21-q22 region (5). Genotype analysis in the Italian PD kindred with additional genetic markers showed recombination events.…”

mentioning

confidence: 99%

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

Polymeropoulos

Lavedan

Leroy

et al. 1997

Science

7,516

5,036

View full text Add to dashboard Cite

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“…Human b-synuclein also was identified, and it is a 134 amino acid long protein with homologies to human a-synuclein (Jakes et al, 1994;Goedert, 1997). However, human a-and b-synucleins are encoded by different genes located on chromosomes 4 (4q21) and 5 (5q35), respectively (Campion et al, 1995;Chen et al, 1995;Shibashi et al, 1995;Spillantini et al, 1995). Further, the bovine homologue of human b-synuclein has been characterized and it is known as phosphoneuronoprotein 14 or PNP14 (Nakajo et al, 1990;Shibayama-Imazu et al, 1993), while the song bird homologue of human synuclein is known as synelfin, and anti-synelfin antibodies crossreact with mammalian synucleins Irizarry et al, 1996;Withers et al, 1997).…”

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confidence: 99%

Fatal attractions: abnormal protein aggregation and neuron death in Parkinson's disease and Lewy body dementia

et al. 1998

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The abnormal aggregation of proteins into fibrillar lesions is a neuropathological hallmark of several sporadic and hereditary neurodegenerative diseases. For example, Lewy bodies (LBs) are intracytoplasmic filamentous inclusions that accumulate primarily in subcortical neurons of patients with Parkinson's disease (PD), or predominantly in neocortical neurons in a subtype of Alzheimer's disease (AD) known as the LB variant of AD (LBVAD) and in dementia with LBs (DLB). Aggregated neurofilament subunits and a-synuclein are major protein components of LBs, and these inclusions may contribute mechanistically to the degeneration of neurons in PD, DLB and LBVAD. Here we review recent studies of the protein building blocks of LBs, as well as the role LBs play in the onset and progression of PD, DLB and LBVAD. Increased understanding of the protein composition and pathological significance of LBs may provide insight into mechanisms of neuron dysfunction and death in other neurodegenerative disorders characterized by brain lesions containing massive deposits of proteinacious fibrils.

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“…Although they are homologous, each synuclein is encoded by a different gene on chromosomes 4q21.3-q22 (␣S) (7,8), 5q35 (␤S) (9), and 10q23 (␥S) (10).…”

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confidence: 99%

Axon pathology in Parkinson’s disease and Lewy body dementia hippocampus contains α-, β-, and γ-synuclein

Galvin

Uryu

Lee

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

405

305

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Pathogenic ␣-synuclein (␣S) gene mutations occur in rare familial Parkinson's disease (PD) kindreds, and wild-type ␣S is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease, but ␤-synuclein (␤S) and ␥-synuclein (␥S) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to ␣S and ␤S reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2͞3 regions, whereas antibodies to ␥S detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the ␣S-and ␤S-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative ''synucleinopathies'' by implicating ␤S and ␥S, in addition to ␣S, in the onset͞progression of PD and DLB.perforant pathway ͉ mossy fibers T he synucleins are a family of soluble presynaptic proteins that are abundant in neurons and include ␣-synuclein (␣S) (also known as the nonamyloid component of plaques precursor protein or NACP) (1, 2), ␤-synuclein (␤S) (also known as phosphoneuroprotein 14 or PNP14) (3, 4), and ␥-synuclein (␥S) (also known as breast cancer-specific gene 1 or BCSG1 and persyn) (5, 6). Although they are homologous, each synuclein is encoded by a different gene on chromosomes 4q21.3-q22 (␣S) (7, 8), 5q35 (␤S) (9), and 10q23 (␥S) (10).The functions of synucleins are poorly understood; however, mutations in the ␣S gene are linked to familial Parkinson's disease (PD) in rare kindreds (11,12). ␣S is a major component of Lewy bodies (LBs) and Lewy neurites in sporadic PD, dementia with LBs (DLB) and a subtype of Alzheimer's disease (AD) with abundant neocortical LBs known as the LB variant of AD (13-15). Further, LBs have been described in familial AD caused by presenilin and amyloid precursor protein gene mutations (16) and Down's syndrome (17). In addition, ␣S is a major component of glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA) (18, 19) as well as the neuronal inclusions and GCIs in Hallervorden-Spatz disease (18). Heretofore, ␤S and ␥S have not been implicated in neurodegenerative disease (15, 18), although ␥S may play a role in breast cancer progression (5).Here, we report the identification of axonal pathology with antibodies to ␤S and ␥S in the hippocampus of PD and DLB brains, but not in control brains, thereby implicating ␤S and ␥S, in addition to ␣S, in neurodegenerative disease. MethodsCase Materials. Brains of autopsy proven PD (n ϭ 5), DLB (n ϭ 5), AD (n ϭ 5), MSA (n ϭ 2), Pick's disease (n ϭ 2), and normal controls (n ϭ 5) were examined and compared after postmortem assessment in the Center for Neurodegenerative Disease Research at the University of Pennsylvania School of Medicine to establish a neuropathological diagnosis in each case (15-18, 20).Immunohistochemistry. Immu...

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The human NACP/α-synuclein gene: chromosome assignment to 4q21.3–q22 and TaqI RFLP analysis

Cited by 115 publications

References 9 publications

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease

Fatal attractions: abnormal protein aggregation and neuron death in Parkinson's disease and Lewy body dementia

Axon pathology in Parkinson’s disease and Lewy body dementia hippocampus contains α-, β-, and γ-synuclein

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