June 29, 2022

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Targeting miR-132 is expected to rejuvenate the brains of Alzheimer patients

Cell Stem Cell: Targeting miR-132 is expected to rejuvenate the brains of patients with Alzheimer’s disease

 

Targeting miR-132 is expected to rejuvenate the brains of Alzheimer patients .  Alzheimer’s disease (AD) is a progressive neurodegenerative disease with insidious onset. The initial symptoms of the clinical manifestations are memory loss, obstacles in daily life, and eventually bedridden, incontinence, and completely dependent on the care of family members. The cause is still unknown.

Onset before 65 years of age is called Alzheimer’s disease; onset after 65 years of age is called Alzheimer’s disease. At present, only drugs can be used to relieve brain atrophy, and there is no cure. The average survival period after diagnosis is 10 years.

AD is the fourth leading cause of death after heart disease, tumor and stroke. It has become one of the biggest challenges facing human beings in global public health and social health care at present and in the future. Current treatment strategies cannot prevent, slow down or cure this pathology.

In a new study, researchers from the Netherlands Institute of Neuroscience have identified a small RNA molecule called miR-132, which can be used to rejuvenate the brains of AD model animals and counteract memory loss. The relevant research results were published online on May 24, 2021 in the journal Cell Stem Cell, with the title of the paper “Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease”.


Recently, it has been confirmed in scientific research that there are cells produced in adulthood in the hippocampus of the elderly. This shows that, generally speaking, the so-called adult neurogenesis process is continuous throughout adulthood. In animal models and humans, adult neurogenesis is related to several aspects of cognition and memory, and it has been reported to be drastically reduced in the brains of AD patients.

The scientists also found that higher levels of adult neurogenesis in these patients appeared to be associated with better cognitive performance before death. This may indicate that adult neurons in the human brain may contribute to the formation of a cognitive reserve that will subsequently provide greater flexibility in preventing memory loss. Therefore, in this new study, the authors investigated whether promoting adult neurogenesis can help prevent or improve dementia in AD.

 

These authors pointed out that seven years ago, when studying miR-132 expressed in the human brain, they made a rather unexpected observation. The small RNA molecules they previously found to be reduced in the brains of AD patients seem to regulate the balance of neural stem cells in the central nervous system. Seven years ago, AD was considered a disease that only affects mature neurons, so at first glance, this finding does not seem to explain the potential role of miR-132 in the progression of AD.

Targeting miR-132 is expected to rejuvenate the brains of Alzheimer patients
Picture from Cell Stem Cell, 2021, doi:10.1016/j.stem.2021.05.001.

In this study, these authors set out to solve whether miR-132 can regulate adult neurogenesis in the hippocampus of healthy brains and AD brains. Using different AD mouse models, human neural stem cells cultured in vitro, and human brain tissue after death, they found that this small RNA molecule is necessary for the neurogenesis process of the adult hippocampus.

Decreasing the level of miR-132 in human neural stem cells in adult mouse brains or petri dishes can impair the production of new neurons. However, restoring miR-132 levels in AD mice can rescue neurogenesis defects and offset the memory impairment associated with adult neurogenesis defects.

 

These authors provide a proof-of-concept for the development of potential therapies to restore adult neurogenesis in AD. The authors’ next goal is to systematically evaluate the effectiveness and safety of targeting miR-132 as an AD treatment strategy.

 

 

 

 

Targeting miR-132 is expected to rejuvenate the brains of Alzheimer patients

(sourceinternet, reference only)


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