Objective: Alzheimer's disease (AD), also known as senile dementia, is a common
neurodegenerative disease characterized by progressive cognitive impairment and personality
changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the
pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression
of AD is still not clearly clarified.
Methods: The protein and mRNA levels were measured by western blot and RNA extraction and
quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and
c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells
were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry
and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were
used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR-
335-5p on the cognitive deficits in APP/PS1 transgenic mice.
Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly
up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain
tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly
inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335-
5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3
and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p
obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved
the cognitive abilities of APP/PS1 mice.
Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by
miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression,
indicating a novel approach for AD treatment.