Remimazolam (RMZ) significantly attenuated Aβ1-42-induced cytotoxicity in hippocampal HT22 cells.
RMZ reduced apoptosis and suppressed the production of reactive oxygen species (ROS).
It decreased lactate dehydrogenase (LDH) release and improved mitochondrial membrane potential.
RMZ enhanced , indicated by an increased LC3-II/LC3-I ratio and elevated Beclin-1 expression.
It also decreased levels of P62 and upregulated and expression.
Knockdown of PINK1 eliminated RMZ's protective effects, indicating a specific mechanism.
Simplified
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the pathological accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau proteins. Remimazolam (RMZ), a novel ultra-short-acting benzodiazepine, exhibits neuroprotective effects by enhancing mitochondrial autophagy independently of traditional GABAergic mechanisms. This study investigates the protective role of RMZ against Aβ1-42-induced neuronal damage through /-mediated . In hippocampal HT22 cells, RMZ significantly attenuated Aβ1-42-induced cytotoxicity, reduced apoptosis, suppressed reactive oxygen species (ROS) production, and decreased lactate dehydrogenase (LDH) release. Moreover, RMZ ameliorated mitochondrial membrane depolarization and tau hyperphosphorylation, while enhancing mitophagy, evidenced by an increased LC3-II/LC3-I ratio, elevated Beclin-1 expression, and decreased P62 levels. Mechanistically, RMZ upregulated PINK1 and Parkin expression, facilitating mitochondrial recruitment and clearance of damaged mitochondria. Importantly, knockdown of PINK1 abolished RMZ's protective effects, confirming the pathway's specificity. These findings suggest that RMZ promotes mitochondrial homeostasis and offers a promising strategy for AD therapy via PINK1/Parkin-mediated mitophagy.
Key numbers
50 of 100
Cell Viability Increase
Cell viability in Aβ + RMZ groups compared to Aβ group.
2.3×
Release Decrease
Comparison of levels in Aβ + RMZ groups vs. Aβ group.
17×
Expression Increase
expression levels in Aβ + RMZ groups compared to Aβ group.
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Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
