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J Alzheimers Dis. 2018;63(2):761-772. doi: 10.3233/JAD-180077.

TRPC1 Null Exacerbates Memory Deficit and Apoptosis Induced by Amyloid-β.

Author information

1
Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Key Laboratory of Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2
Key Laboratory of Modern Toxicology of Shenzhen, and Center for Disease Control and Prevention, Shenzhen, China.
3
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Abstract

The transient receptor potential cation (TRPC) channels are widely expressed in nervous system but their functions remain largely unclear. Here, we found that TRPC1 deletion did not affect learning and memory in physiological conditions, while it aggravated learning and memory deficits induced by amyloid-β (Aβ), the major component of the senile plaques observed in the brains of Alzheimer's disease (AD). Further studies demonstrated that TRPC1 deletion did not affect cell apoptosis in physiological condition, but it exacerbated the Aβ-induced cell death in mouse hippocampus. Moreover, the level of TRPC1 was decreased in AD cell and mouse models, and upregulation of TRPC1 decreased Aβ levels with attenuation of apoptosis in the cells stably overexpressing amyloid-β protein precursor (AβPP). Finally, the transmembrane domain of TRPC1 could bind to AβPP and thus decreased Aβ production. These findings indicate that loss of TRPC1 exacerbates Aβ-induced memory deficit and cell apoptosis, though it does not impair cognitive function or induce cell death in physiological conditions.

KEYWORDS:

Alzheimer’s disease; amyloid-β; apoptosis; cognitive impairment; transient receptor potential channels

PMID:
29660945
DOI:
10.3233/JAD-180077
[Indexed for MEDLINE]

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