絞り込み

16638

広告

Lysosomal trafficking defects link Parkinson's disease with Gaucher's disease.

著者 Wong YC , Krainc D
Mov Disord.2016 Sep 13 ; ():.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

スターを付ける スターを付ける     (175view , 1users)

Full Text Sources

Medical

Other Literature Sources

Lysosomal dysfunction has been implicated in multiple diseases, including lysosomal storage disorders such as Gaucher's disease, in which loss-of-function mutations in the GTP-binding protein type A1 (GBA1) gene encoding the lysosomal hydrolase β-glucocerebrosidase result in lipid substrate accumulation. In Parkinson's disease, α-synuclein accumulates in Lewy bodies and neurites contributing to neuronal death. Previous clinical and genetic evidence has demonstrated an important link between Parkinson's and Gaucher's disease, as GBA1 mutations and variants increase the risk of Parkinson's and Parkinson's patients exhibit decreased β-glucocerebrosidase activity. Using human midbrain neuron cultures, we have found that loss of β-glucocerebrosidase activity promotes α-synuclein accumulation and toxicity, whereas α-synuclein accumulation further contributes to decreased lysosomal β-glucocerebrosidase activity by disrupting β-glucocerebrosidase trafficking to lysosomes. Moreover, α-synuclein accumulation disrupts trafficking of additional lysosomal hydrolases, further contributing to lysosomal dysfunction and neuronal dyshomeostasis. Importantly, promoting β-glucocerebrosidase activity reduces α-synuclein accumulation and rescues lysosomal and neuronal dysfunction, suggesting that β-glucocerebrosidase may be an important therapeutic target for advancing drug discovery in synucleinopathies including Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society.
PMID: 27619775 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード