micro RNA-124 in Frontotemporal dementia (FTD)

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Frontotemporal dementia (FTD) is a well-known neurodegenerative disease after Alzheimer’s. FTD is a kind of dementia that causes gradual and long term decrease in the ability to think, remember and perform daily activities. FTD is named so, as the patients show degeneration and dysfunction of neurons in the frontal, temporal and subcortical regions of the brain. Mostly the onset of the disease is around 60 years of age leading to dementia and death gradually in a span of 8 to 9 years. No effective treatments are available till date. Of the several genes associated with this disease are CHMP2B (encoding charged multivesicular body protein 2B), a highly conserved component of the ESCRT-III (endosomal sorting complex required for transport) complex involved in endosomal trafficking. Mutations in this gene leads to a truncated protein that results in disrupted neuronal function associated with this disease. The mechanisms involved in the disease process are not clear.

In a study by the research team led by Prof.Fen-Biao Gao, at University of Massachusetts Medical school, a mouse model for FTD that express mutant CHMP2B, showed normal sociability at 2 months of age, whereas from 4 to 8 months old they displayed decreased sociability unlike the mice without CHMP2B mutation. The study was based on a simple test to determine the sociability by investigating the amount of time spent by a mice in an unfamiliar cage. The CHMP2B mutant mice appeared to spend the least time investigating an unfamiliar cage suggesting decreased sociability. This study further revealed interesting mechanisms underlying the social dysfunction observed in CHMP2B mutant mice. The researchers observed a downregulation of a micro RNA, miR-124 in the cortex of CHMP2B mutant mouse brain. miR-124 is brain enriched micro RNA playing a prominent role in the function and maintenance of healthy neurons. This downregulation progressed from 4 to 8 weeks on par with the increasing GLUA2, GLUA3, GLUA4 and so was the social dysfunction. GLUA2, GLUA3 and GLUA4 are the subunits of AMPA receptors that maintain a calcium balance in the neuronal cells required for nerve transmission. In the study, miR-124 was shown to reduce GLUA2 and GLUA4 levels and corrected the sociability deficits in CHMP2B mutant mice. Frontal cortex tissue samples and neuronal cell cultures harvested from the postmortem of FTD patients showed similar observation as in the CHMP2B mutant mice.

However, the underlying mechanisms downregulating the levels of miR-124 in CHMP2B mutants are yet to be investigated. This study however provides hope for the development of microRNA based therapies for FTD patients.

Source:

http://www.nature.com/nm/journal/v20/n12/full/nm.3717.html

Disclaimer: This article does not reflect any personal views of authors/editors

1 COMMENT

  1. I studied lot about fronto temporal dementia..my mum hv tis pblm past 9 years ..v care a lot lk a child…nowadays she remember our names nd she saying our family member names also but she dono who thy r…v hope tat she s recovering..it s possible to cure r not…plz i need a answer.