title: Altered expression of autophagic genes in the peripheral leukocytes of patients with sporadic Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disease caused by interaction of genetic and environmental factors. To date, genetic genes and variants causing PD remain largely unknown. Autophagy is a conserved cellular process including three subtypes, macroautophagy (hereafter referred to as autophagy), microautophagy and chaperone-mediated autophagy (CMA). Although reduced CMA and induced autophagy are observed in human PD brain samples, cell and animal PD models, CMA and autophagy have not been systemically studied in sporadic PD patients. In the peripheral leukocytes of sporadic PD patients, we examined gene expression levels of lysosome-associated membrane 2 (LAMP-2), a CMA receptor and a limiting step, and microtubule-associated protein 1 light chain 3 (LC3), product of which is sequentially cleaved and lipidated to form LC3-II as an autophagosome marker. Compared to age- and sex-matched healthy controls, LAMP-2 gene expression and protein levels in sporadic PD patients were significantly decreased, which may lead to reduced CMA activity and impaired fusion of autophagosome and lysosome. LC3 gene expression and LC3-II protein levels were significantly increased in sporadic PD patients, suggesting that autophagosomes are accumulated. Our findings, decreased LAMP-2 gene expression and increased LC3 gene expression, are consistent to the previous studies with dopaminergic neuronal cells in vitro and in vivo, which may contribute to the pathogenesis of sporadic PD by altering CMA and autophagy activities. The genetic causes leading to decreased LAMP-2 gene expression need further investigation and genetic or pharmacological restoration of LAMP-2 might be a novel strategy for treating PD patients.
authors.affiliation: Division of Cardiac Surgery, Jining Medical College Affiliated Hospital, Jining Medical College, Jining, Shandong 272029, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Wu
authors.forename: Xuenan
authors.initials: X
authors.lastname: Wang
authors.forename: Xungang
authors.initials: X
authors.lastname: Feng
authors.forename: Aimei
authors.initials: A
authors.lastname: Zhang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Li
authors.forename: Kejin
authors.initials: K
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.forename: Haixin
authors.initials: H
authors.lastname: Dong
authors.forename: Huijie
authors.initials: H
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D001343:Autophagy / Q000235:genetics*; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000096:biosynthesis*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D018832:Molecular Chaperones / Q000096:biosynthesis; D010300:Parkinson Disease / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones