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Chaperone and anti‐chaperone: Two‐faced synuclein as stimulator of synaptic evolution
Author(s) -
Fujita Masayo,
Wei Jianshe,
Nakai Masaaki,
Masliah Eliezer,
Hashimoto Makoto
Publication year - 2006
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/j.1440-1789.2006.00732.x
Subject(s) - chaperone (clinical) , neurodegeneration , biology , microbiology and biotechnology , protein aggregation , phenotype , unfolded protein response , neuroscience , genetics , gene , disease , endoplasmic reticulum , medicine , pathology
Previous studies have shown that β‐synuclein (β‐syn), the homologue of α‐syn, inhibited α‐syn aggregation and stabilized Akt cell survival signaling molecule, suggesting that β‐syn was protective against α‐syn‐related neurodegenerative disorders, such as Parkinson’s disease and diffuse Lewy body disease. However, emerging evidence argues that the situation may be not so simple. Two missense mutations of β‐syn were identified in familial and sporadic diffuse Lewy body disease, and wild type β‐syn was induced to form fibril structures in vitro, while, α‐syn was shown to be protective against neurodegeneration caused by deletion of cysteine‐string protein‐α, the presynaptic cochaperone to Hsc70 in mice. Collectively, α‐ and β‐syn are both, but in varying degrees, featured with two opposite properties, namely normal chaperone and anti‐chaperone. By reviewing recent progress in syn biology with a particular focus on β‐syn, this manuscript refers to the intriguing possibility that the dual syn proteins might have acquired a driving force for synaptic evolution. Hypothetically, the anti‐chaperone syn may provoke stress‐induced diverse responses, whereas, the chaperone syn may provide buffering for them, allowing accumulation of nonlethal phenotypic variations in synapses. Consequently, dual syn proteins may cope with forth‐coming stresses in the brain by stimulating adaptive evolution. In this context, failure to regulate this process due to various causes, such as gene mutations and environmental risk factors, may result in imperfect adaptability against stresses, leading to neurodegenerative disorders.