MicroRNA-922 Downregulates Ubiquitin Carboxy-terminal Hydrolase L1(UCHL1) Expression In The Pathogenesis Of Alzheimer’s Disease

Alzheimer’s disease(AD) is one of the most common and lethal neurodegenerative disorder,classified as either early onset(under 65 years of age), or late onset(over 65 years of age). The major hallmarks of Alzheimer’s disease are extracellular aggregation of amyloid β peptides and, the presence of intracellular neurofibrillary tangles formed by precipitation/aggregation of hyperphosphorylated tau protein. Multifactorial factors such as genetic, age-related and environmental factors contribute the etiology of Alzheimer’s disease and a full understanding of its pathogenesis remains elusive.Decreased levels of soluble UCHL1 have been reported in the brains of sporadic Alzheimer’s disease(AD) patients, and the introduction of Ubiquitin carboxy-terminal hydrolase L1(UCHL1) rescued the synaptic and cognitive function of AD model mice. Obviously, a reduction in the levels of UCHL1 may play a role in the pathogenesis of AD. However, the mechanisms underlying the regulation of UCHL1 levels in AD were unknown.Neurofibrillary tangles(NFTs) mainly consisting of the hyperphosphorylated microtubule associated protein tau are the defining pathological features of AD. In the present study, we found the levels of UCHL1 affected the levels of phosphorylated tau: the phosphorylated tau levels increased when UCHL1 expression was knockdown, and the phosphorylated tau levels decreased when UCHL1 was overexpressed.Many microRNAs(miRs) have been shown to participate in the process of AD, In our study, we discovered that microRNA-922 decreased the levels of UCHL1, furthermore, overexpression of micro RNA-922 increased the phosphorylated tau levels.In conclusion, miR-922 increasing the levels of phosphorylated tau by regulating UCHL1 levels contributed to the pathogenesis of AD. Our study partly explained one of the mechanisms underlying the downregulation of UCHL1 levels in AD patients and could enrich the content of tau theory in the pathogenesis of AD.