The G209A Mutation in the α-Synuclein Gene Is Not Detected in Familial Cases of Parkinson Disease in Non-Greek and/or Italian Populations

Wang, William W.; Khajavi, Mehrdad; Patel, Bhavna J.; Beach, Jordan R.; Jankovic, Joseph; Ashizawa, Tetsuo

doi:10.1001/archneur.55.12.1521

Cited by 34 publications

(16 citation statements)

References 17 publications

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“…The discovery of another missense mutation in the h-synuclein gene [nucleotide change G88C, resulting in an Ala30Pro (A30P) exchange] associated with autosomal dominant PD in a German family [61] reinforced the hypothesis that these mutations are involved in the pathogenesis of PD. Subsequently, however, searches for these two mutations in the h-synuclein gene in many familial (dominant and recessive), sporadic, and early-onset PD patients have proven unsuccessful [62][63][64][65][66][67][68][69]. Other mutations in the h-synuclein gene have also been sought: the entire coding region of h-synuclein (using as templates either cDNA or genomic DNA including exon/ intron boundaries) was sequenced in 61 autosomal dominant PD families [64,70,71], in 21 PD patients with at least one affected first-degree relative [72,73], in 7 isolated PD cases [73], and in 24 pathologically proven sporadic PD cases [74].…”

Section: Geneticsmentioning

confidence: 99%

Alpha-synuclein and Parkinson's disease

Lücking¹,

Brice²

2000

CMLS, Cell. Mol. Life Sci.

263

215

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The involvement of alpha-synuclein in neurodegenerative diseases was first suspected after the isolation of an alpha-synuclein fragment (NAC) from amyloid plaques in Alzheimer's disease (AD). Later, two different alpha-synuclein mutations were shown to be associated with autosomal-dominant Parkinson's disease (PD), but only in a small number of families. However, the discovery that alpha-synuclein is a major component of Lewy bodies and Lewy neurites, the pathological hallmarks of PD, confirmed its role in PD pathogenesis. Pathological aggregation of the protein might be responsible for neurodegeneration. In addition, soluble oligomers of alpha-synuclein might be even more toxic than the insoluble fibrils found in Lewy bodies. Multiple factors have been shown to accelerate alpha-synuclein aggregation in vitro. Therapeutic strategies aimed to prevent this aggregation are therefore envisaged. Although little has been learned about its normal function, alpha-synuclein appears to interact with a variety of proteins and membrane phospholipids, and may therefore participate in a number of signaling pathways. In particular, it may play a role in regulating cell differentiation, synaptic plasticity, cell survival, and dopaminergic neurotransmission. Thus, pathological mechanisms based on disrupted normal function are also possible.

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Section: Geneticsmentioning

confidence: 99%

Alpha-synuclein and Parkinson's disease

Lücking¹,

Brice²

2000

CMLS, Cell. Mol. Life Sci.

263

215

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“…[19] Many studies conducted worldwide related to the pathogenicity of SNCA gene in PD reveal the lack of mutations. [20][21][22][23][24][25] India is known for high degree of inbreeding with its heterogynous population. This makes it necessary to screen a large number of patients perhaps within each group in order to get a true picture of contribution of SNCA gene mutation to PD.…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of α-synuclein gene in Parkinson′s disease in North Karnataka, India

Kadakol

Kulkarni²,

Wali³

et al. 2014

Neurol India

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“…Hence, it is likely that aberrant syn ap tic func tions may directly lead to neurodegeneration sim i lar to sev eral other neurodegenerative diseases (Table 1). How ever, sev eral stud ies have failed to detect mutations in alpha-synuclein in a large num ber of other fam i lies and sporadic cases (65)(66)(67). In addi tion, the muta tion iden ti fied in PD patients at codon 53 (Ala 53 Thr) is also present in mouse, rat, and canary alpha-synuclein (Fig.…”

Section: Ge Netic Con Tri Bu Tions To Pdmentioning

confidence: 99%

Molecular Etiology of Parkinson Disease: Recent Progress

Shastry

2000

Neuroscientist

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Parkinson disease (PD) is one of the most widespread neurodegenerative disorders. In North America alone it affects 1 million people. It is a multifactorial disorder caused by genetic, various biological and environmental factors. One of the important features of PD is the dementia, which is believed to be due to the loss of dopaminergic neurons. In some cases the disease can be inherited as an autosomal dominant or recessive trait but in the majority of cases it is acquired. The biological causes of the disorder are unknown. The identification of mutations in the parkin gene in the autosomal recessive case and alpha-synuclein gene in autosomal dominant cases has opened a new avenue for studies to understand the basic biochemical mechanisms of pathogenesis. Although several types of treatments such as transplantation of cells that produce L-Dopa and direct gene delivery using adeno-associated viral vectors may correct animal models of PD, their usefulness in the human is not yet clear. A better understanding of the causes of neurodegeneration may lead to better therapies in the future.

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The G209A Mutation in the α-Synuclein Gene Is Not Detected in Familial Cases of Parkinson Disease in Non-Greek and/or Italian Populations

Abstract: The G209A mutation is rare in US patients with familial PD.

Cited by 34 publications

References 17 publications

Alpha-synuclein and Parkinson's disease

Alpha-synuclein and Parkinson's disease

Molecular analysis of α-synuclein gene in Parkinson′s disease in North Karnataka, India

Molecular Etiology of Parkinson Disease: Recent Progress

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