Abstract
MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals with Alzheimer’s disease (AD) as compared to those of healthy elderly adults. Some of the miRNAs found to be dysregulated in AD have been reported to correlate with neuropathological changes, including plaque and tangle accumulation, as well as altered expressions of species that are known to be involved in AD pathology. To examine the potentially pathogenic functions of several dysregulated miRNAs in AD, we review the current literature with a focus on the activities of ten miRNAs in biological pathways involved in AD pathogenesis. Comprehensive understandings of the expression profiles and activities of these miRNAs will illuminate their roles as potential therapeutic targets in AD brain and may lead to the discovery of breakthrough treatment strategies for AD.
Highlights
As of 2015, 47 million people worldwide are estimated to be living with dementia, 9.9 million people are estimated to be diagnosed with dementia each year, and the global costs of the disease are estimated to be 818 billion United States dollars (USD$)
In the context of this information, we review ten widely studied dysregulated miRNAs in Alzheimer’s disease (AD), concentrating on their altered expressions in AD and their participation in pathways that appear to contribute to AD pathology
Multiple studies have shown increased the production of amyloid precursor protein (APP), γ-secretase, BACE-1 and Aβ in neurons exposed to neurotoxic concentrations of Aβ, which suggests that the neuroinflammatory response in AD facilitates a positive feedback mechanism for the production of
Summary
As of 2015, 47 million people worldwide are estimated to be living with dementia, 9.9 million people are estimated to be diagnosed with dementia each year, and the global costs of the disease are estimated to be 818 billion United States dollars (USD$). Dementia caused by AD is broadly characterized by the deterioration of memory and cognition with age. AD is characterized by overproduction of the 40 and 42 amino acid isoforms of β-amyloid (Aβ1–40 and Aβ1–42 ), which form insoluble, extracellular aggregates of Aβ called amyloid plaques, and by the hyperphosphorylation and aggregation of the microtubule-associated protein tau within neurons. These insoluble, intracellular aggregates are called neurofibrillary tangles (NFTs). NFTs, and neuroinflammation have been hypothesized to be neurotoxic and responsible for the loss of neurons and synapses in AD brain, the precise cause and sequence of AD pathogenesis remains controversial. We overview several drug classes with potential to target and manipulate miRNA activity, and hold promise as future therapeutics for AD treatment
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