TY - JOUR
T1 - Subcellular localization of α-synuclein in primary neuronal cultures
T2 - Effect of missense mutations
AU - McLean, P. J.
AU - Ribich, S.
AU - Hyman, B. T.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - Numerous recent observations have implicated α-synuclein in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, dementia with Lewy bodies and multiple-system atrophy. Two missense mutations in the gene for α-synuclein have been identified in some cases of familial Parkinson's disease and it is thought that these may disrupt the normal structure of the protein and thus promote aggregation into Lewy body filaments. Here, we examine the subcellular localization of α-synuclein in primary cortical neurons maintained in a monolayer culture. The protein has widespread expression throughout neurons, including the nucleus, and has a discete localization in the neurites of more mature neurons, reminiscent of synaptic specializations. Interestingly, in a subpopulation of cortical neurons transfected at 13 days in vitro, we find that α-synuclein appears to aggregate into distinct punctate inclusions in the cytoplasm and proximal neurites. Unlike Lewy bodies, these structures are not ubiquitin positive. These regions of α-synuclein accumulation are observed following transfections with wild-type, Ala30Pro or Ala53Thr α-synuclein; neither mutation alters their frequency.
AB - Numerous recent observations have implicated α-synuclein in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, dementia with Lewy bodies and multiple-system atrophy. Two missense mutations in the gene for α-synuclein have been identified in some cases of familial Parkinson's disease and it is thought that these may disrupt the normal structure of the protein and thus promote aggregation into Lewy body filaments. Here, we examine the subcellular localization of α-synuclein in primary cortical neurons maintained in a monolayer culture. The protein has widespread expression throughout neurons, including the nucleus, and has a discete localization in the neurites of more mature neurons, reminiscent of synaptic specializations. Interestingly, in a subpopulation of cortical neurons transfected at 13 days in vitro, we find that α-synuclein appears to aggregate into distinct punctate inclusions in the cytoplasm and proximal neurites. Unlike Lewy bodies, these structures are not ubiquitin positive. These regions of α-synuclein accumulation are observed following transfections with wild-type, Ala30Pro or Ala53Thr α-synuclein; neither mutation alters their frequency.
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U2 - 10.1007/978-3-7091-6284-2_5
DO - 10.1007/978-3-7091-6284-2_5
M3 - Article
C2 - 11128613
AN - SCOPUS:0033724436
SN - 0303-6995
SP - 53
EP - 63
JO - Journal of Neural Transmission, Supplement
JF - Journal of Neural Transmission, Supplement
IS - 58
ER -