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

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.

• Authors: Mengzhu Li, Enjie Liu, Qiuzhi Zhou, Shihong Li, Xin Wang, Yanchao Liu, Lin Wang, Dongsheng Sun, Jinwang Ye, Yuan Gao, Xifei Yang, Jianjun Liu, Ying Yang, Jian-Zhi Wang
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 63 Issue 2 Pg. 761-772 ( 2018) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 29660945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• TRPC Cation Channels
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• transient receptor potential cation channel, subfamily C, member 1

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Apoptosis (physiology)
• Cell Line, Tumor
• Disease Models, Animal
• HEK293 Cells
• Hippocampus (metabolism, pathology)
• Humans
• Learning (physiology)
• Male
• Memory (physiology)
• Memory Disorders (metabolism, pathology)
• Mice, 129 Strain
• Mice, Knockout
• Peptide Fragments (metabolism)
• Protein Domains
• TRPC Cation Channels (deficiency, genetics)