MicroRNAs (miRNAs) are small non-coding nucleic acids that are able to inhibit the target messenger RNAs (mRNAs). MiRNAs regulate the neurite outgrowth, neuronal differentiation, and synaptic plasticity in the brain, and dysfunctioning miRNAs are increasingly recognized in Alzheimer’s disease (AD) research.
As the research fields of miRNAs as diagnostic biomarkers and therapeutic agents are rapidly growing, miRNAs can be used for the disease staging and risk prediction and also be expected to offer certain potential options as therapeutic agents.
Various miRNAs have been found to be either up-regulated or down-regulated in AD. Some miRNAs contribute to the increase in AD pathologies; in contrast others bring about the opposite effects.
Among the up-regulated miRNAs that are detrimental to AD are miR-204 and miR-155. MiR-204 down-regulates EphB2 (Ephrin type-B receptor 2), resulting in neuronal and cognitive dysfunction; and miR-155 reduces SOCS-1 (suppressor of cytokine signaling-1), activating microglia and astrocytes.
ANL-101, developed by ANLBIO, restored EphB2 by targeting miR-204, and thereby reduced neuroinflammation, neuronal injury, and cognitive deficits in the AD animal models.
ANLBIO, headquartered in Suwon, South Korea, is a biotechnology company developing its innovative miRNA-based gene therapy for neurodegenerative diseases using its proprietary AAV (Adeno-associated virus) vector platform as a delivering vehicle.
Meanwhile, ANLBIO’s ANL-101 was designated as one of preclinical dementia studies by the Korea Dementia Research Center in December 2020 and granted the U.S. patent for a candidate drug for AD in July 2020.
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Danka Mohammed CP, Park JS, Nam HG, Kim K. MicroRNAs in brain aging. Mech Ageing Dev. 2017 Dec;168:3-9.
https://doi.org/10.1016/j.mad.2017.01.007
Mohammed CP, Rhee H, Phee BK, Kim K, Kim HJ, Lee H, Park JH, Jung JH, Kim JY, Kim HC, Park SK, Nam HG, Kim K. miR-204 downregulates EphB2 in aging mouse hippocampal neurons. Aging Cell. 2016 Apr;15(2):380-8.
https://doi.org/10.1111/acel.12444