Neuroprotective effects of chitinase-1 and calcitonin gene-related peptide on Alzheimer's disease by promoting lysosomal function.

Abstract

Background: The amyloid cascade hypothesis still dominates in Alzheimer's disease (AD), and the acceleration of the clearance efficiency of amyloid-β (Aβ) has been always considered as an effective treatment option to slow the occurrence and progression of AD.

Objective: This study aims to explore the role of zkscan3 and its related pathways in AD of the microglia-mediated pathogenesis, and whether the combined effect of drugs can exert neuroprotective function.

Methods: N9 mouse microglia and HT-22 mouse hippocampal neurons were randomly divided into 6 groups, qRT-PCR technique was used to detect the gene expression level of zkscan3 and the genes related to lysosome generation and function. Fourteen C57 mice were randomly divided into two groups, and drug intervention model mice were randomly selected to establish from the AD group. Transmission electron microscope was used to detect the cell status and lysosome function in the hippocampus together with the other two groups.

Results: Compared with the AD model group, the gene expression of zkscan3 in the drug intervention group was downregulated, and the degree of neuronal injury in the hippocampus was reduced, the structure and number of synapses were improved, and the function of intracellular lysosome was enhanced.

Conclusions: Zkscan3 and its related genes play a vital role in the development of AD. CGRP and CHIT-1, as a combined intervention, imparts effects through zkscan3-related pathways to improve lysosomal function and exert certain neuroprotective effects.