SIRT1 Interacts with Prepro-Orexin in the Hypothalamus in SOD1G93A Mice

Gan Zhang; Rong Liu; Zhaofu Sheng; Yonghe Zhang; Dongsheng Fan

doi:10.3390/brainsci12040490

SIRT1 Interacts with Prepro-Orexin in the Hypothalamus in SOD1G93A Mice

Brain Sci. 2022 Apr 11;12(4):490. doi: 10.3390/brainsci12040490.

Authors

Gan Zhang^{1

2}, Rong Liu^{1

2}, Zhaofu Sheng^{2

3}, Yonghe Zhang^{2

3}, Dongsheng Fan^{1

2}

Affiliations

¹ Department of Neurology, Peking University Third Hospital, Beijing 100191, China.
² Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Disease, Beijing 100191, China.
³ Department of Pharmacology, School of Basic Medical Science, Peking University, Beijing 100191, China.

Abstract

The participation of silent mating type information regulation 2 homolog 1 (SIRT1) in amyotrophic lateral sclerosis (ALS) has been reported in many studies. However, the role of the expression and function of SIRT1 in the hypothalamus in ALS remains unknown. In the current study, we performed western blot, co-immunoprecipitation and immunofluorescence analyses to determine the expression and in-depth mechanism of SIRT1 in the hypothalamus in SOD1G93A transgenic mice. We found that SIRT1 was overexpressed in the hypothalamus after motor symptom onset. In addition, SIRT1 interacted with prepro-orexin, a molecule involved in energy balance and the sleep/wake cycle, in both preclinical and clinical ALS regardless of whether SIRT1 levels were elevated. These findings indicate that SIRT1 might participate in sleep and metabolic changes in ALS, suggesting that SIRT1 is a new target for ALS treatment.

Keywords: SIRT1; SOD1G93A mice; amyotrophic lateral sclerosis; prepro-orexin.

Abstract

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