Furthermore, Ucn1 mRNA in males was nearly 10 times and 1.6 times higher than in females in di-and pro-estrus, respectively, indicating a sex-dependent difference in Ucn1 biosynthetic activity. Since, at the same time, immunocytochemistry revealed that the amount of Ucn1 peptide stored in the cell bodies of the npEW-Ucn1 neurons did not differ between males and females, as judged on the basis of the number and immunosignal density of these neurons, we propose that the rate of axonal Ucn1 transport and, possibly, the strength of Ucn1 secretion, are dependent on sex to the same degree
as is Ucn1 biosynthesis. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the selective loss of
dopaminergic neurons and the presence of Lewy bodies. alpha-Synuclein is a major component of Lewy buy S63845 bodies. Recently, many studies have focused on the interaction between alpha-synuclein and catecholamine in the pathogenesis of PD. However, no detailed relationship between cathecholamine and alpha-synuclein cytotoxicity has been elucidated. Therefore, this study established PC12 cell lines which overexpress human alpha-synuclein in a tetracycline-inducible manner. buy PRI-724 The overexpression of human alpha-synuclein increased the number of apoptotic cells in a long-term culture. Moreover, human alpha-synuclein expressing PC12 cells demonstrated an increased vulnerability to several stressors in a short culture period. Thapsigargin increased the SIDS soluble oligomers of alpha-synuclein associated with catecholamine-quinone. The unfolded protein response (UPR) study showed that thapsigargin
increased eIF2 alpha phosphorylation and nuclear GADD153/CHOP induction under alpha-synuclein overexpressed conditions. The activities of the ATF6 alpha and IRE1 alpha pathways Galeterone decreased. These findings suggest that an overexpression of alpha-synuclein partly inactivates the UPR. alpha-Methyltyrosine inhibited the dysfunction of the UPR caused by an overexpression of human alpha-synuclein. Therefore, these findings suggest that the coexistence of human alpha-synuclein with catecholamine enhances the endoplasmic reticulum stress-related toxicity in PD pathogenesis. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Neuronal intranuclear inclusions (NIIs) are the pathological hallmark of polyglutamine (polyQ) diseases. We previously found that the RNA-binding protein FUS/TLS is the major component of nuclear polyQ aggregates of a cellular model of Huntington disease. In this study, we revealed that FUS/TLS binds to NIIs in the human brains from patients with spinocerebellar ataxia type 1, 2, 3, and dentatorubral-pallidoluysian atrophy. Recent reports have revealed that mutations in FUS/TLS gene are responsible for familial amyotrophic lateral sclerosis 6 (ALS6).