The role of sequestosome 1/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis
Adriana Delice Foster1
Sarah Lyn Rea2
1.Harry Perkins Institute of Medical Research,University of Western Australia2.Perron Institute for Neurological and Translational Science,Centre for Neuromuscular and Neurological Disorders,The University of Western Australia,Nedlands,Western Australia,Australia
摘要：Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are multifaceted diseases with geno-typic, pathological and clinical overlap. One such overlap is the presence of SQSTM1/p62 mutations. While traditionally mutations manifesting in the ubiquitin-associated domain of p62 were associated with Paget's disease of bone, mutations affecting all functional domains of p62 have now been identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients. p62 is a multifunctional protein that fa-cilitates protein degradation through autophagy and the ubiquitin-proteasome system, and also regulates cell survival via the Nrf2 antioxidant response pathway, the nuclear factor-kappa B signaling pathway and apoptosis. Dysfunction in these signaling and protein degradation pathways have been observed in amy-otrophic lateral sclerosis and frontotemporal lobar degeneration, and mutations that affect the role of p62 in these pathways may contribute to disease pathogenesis. In this review we discuss the role of p62 in these pathways, the effects of p62 mutations and the effect of mutations in the p62 modulator TANK-binding kinase 1, in relation to amyotrophic lateral sclerosis-frontotemporal lobar degeneration pathogenesis.
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论文发表日期：2020-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 2186-2194 )
英文信息