{"corpus_id":82861981,"paper_sha":"cbc017a673a4de493b90533b6ea82d1df02d8ae5","doi":"10.5772/16671","arxiv_id":null,"pmid":null,"pmcid":null,"mag_id":1568749868,"dblp_id":null,"acl_id":null,"title":"The Hsp70 Chaperone System in Parkinson’s Disease","year":2011,"publication_date":"2011-10-12","venue":"","journal":{"name":"","pages":null,"volume":""},"journal_issn":null,"journal_title":null,"publication_types":[],"pubmed_pub_types":null,"s2_fields_of_study":["Biology","Medicine"],"reference_count":219,"citation_count":8,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":null,"chemicals":null,"comments_corrections":null,"source_flags":1,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Several neurodegenerative diseases are associated with a build up of misfolded or abnormal proteins and the formation of distinct aggregates, resulting in a putative pathological protein load on the nervous system (Chiti & Dobson, 2006). This aberrant accumulation of amyloid or amyloid-like aggregates occurs in Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s (HD) diseases, amyotrophic lateral sclerosis, and frontotemporal dementia, among others. A broad array of cellular defence mechanisms operate to counteract this effect, including antioxidant proteins, the stress-inducible response and, in particular, molecular chaperones (Morimoto, 2008; Voisine et al., 2010). Molecular chaperones are responsible for maintaining normal protein homeostasis within the cell by assisting protein folding, inhibiting protein aggregation, and modulating protein degradation pathways (Hartl & Hayer-Hartl, 2009). Currently, there is substantial evidence supporting the involvement of these protein aggregational processes and a role of molecular chaperones, and especially of Hsp70, in PD pathogenesis (Bandopadhyay & de Belleroche, 2010; Broadley & Hartl, 2009; Witt, 2009). Firstly, extensive colocalization of Hsp70 with αsynuclein (αSyn), the major component of Lewy bodies (LBs) (Spillantini et al., 1998), within the intraneuronal inclusions in PD brains has been demonstrated (Auluck et al., 2002; McLean et al., 2002). Secondly, patients with PD show highly perturbed expression of different members of the Hsp70 family in the substantia nigra pars compacta (SN) of the brain, which is precisely the target of neurodegeneration (Grunblatt et al., 2001; Hauser et al., 2005). Finally, there is a considerable amount of data derived from studies performed in vitro, in cell culture and with animal models of PD (Arawaka et al., 2010; Witt, 2009), that support the protective effects of Hsp70 against αSyn aggregation and toxicity, considered to be central in the aetiology of the disease. The discovery within the last few years of three different missense mutations (A30P, E46K and A53T) in the αSyn gene as causative of early onset PD unambiguously linked this protein to disease onset and progression (Kruger et al., 1998; Polymeropoulos et al., 1997; Zarranz et al., 2004). Additionally, a locus triplication causing an increased dosage of the wild-type฀ (Wt)฀αSyn gene has been found to potentiate neurodegeneration (Singleton et al.,","claims":[{"public_id":"cl_c6a05830a685b24d455ce48a3e0aca73","status":"active","text":"A triplication of the wild-type α-synuclein locus increases gene dosage and potentiates neurodegeneration.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_c6a05830a685b24d455ce48a3e0aca73"},{"public_id":"cl_26d77016c51a53899916d0c38efa9cfb","status":"active","text":"Extensive colocalization of Hsp70 with α-synuclein within intraneuronal inclusions has been demonstrated in Parkinson’s disease brains.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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