title: Myristic acid hitchhiking on sigma-1 receptor to fend off neurodegeneration.
abstract: Neurodegenerative diseases are linked to tauopathy as a result of cyclin dependent kinase 5 (cdk5) binding to its p25 activator instead of its p35 activator and becoming over-activated. The overactive complex stimulates the hyperphosphorylation of tau proteins, leading to neurofibrillary tangles (NFTs) and stunting axon growth and development. It is known that the sigma-1 receptor (Sig-1R), an endoplasmic reticulum chaperone, can be involved in axon growth by promoting neurite sprouting through nerve growth factor (NGF) and tropomyosin receptor kinase B (TrkB)[1, 2]. It has also been previously demonstrated that a Sig-1R deficiency impairs the process of neurogenesis by causing a down-regulation of N-methyl-D-aspartate receptors (NMDARs)[3]. The recent study by Tsaiet al. sought to understand the relationship between Sig-1R and tauopathy[4]. It was discovered that the Sig-1R helps maintain proper tau phosphorylation and axon development by facilitating p35 myristoylation and promoting p35 turnover. Neurons that had the Sig-1R knocked down exhibited shortened axons and higher levels of phosphorylated tau proteins compared to control neurons. Here we discuss these recent findings on the role of Sig-1R in tauopathy and highlight the newly presented physiological consequences of the Sig-1R-lipid interaction, helping to understand the close relationship between lipids and neurodegeneration.
authors.affiliation: Cellular Pathobiology Section, Integrative Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Ciesielski
authors.affiliation: Cellular Pathobiology Section, Integrative Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.
authors.forename: Tsung-Ping
authors.initials: TP
authors.lastname: Su
authors.affiliation: Cellular Pathobiology Section, Integrative Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Tsai