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September 20, 2017

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Possible cure for dementia found by researchers

The China Post news staff--A National Cheng Kung University (NCKU) research team has discovered that rapamycin, an autophagy activator drug, may be used to alleviate frontotemporal lobar degeneration (FTLD), one of the main causes of dementia.

The medical breakthrough made by the team led by Kuen-Jer Tsai, professor at the Institute of Clinical Medicine and Institute of Basic Medical Science, NCKU, was published in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on Sept. 11.

The activation of autophagy, the process of self-digestion by a cell, is the crucial discovery of the research, according to Tsai, adding that autophagy activators alleviate pathogensis of mice with proteopathy related to the TAR DNA-binding protein 43 (TDP-43).

Among those aged 65 and above, FTLD is the fourth most common cause of dementia, after Alzheimer's disease, Lewy body dementia and vascular dementia.

FTLD, however, is the second most common cause of dementia below Alzheimer's in patients less than 65 years old, according to the team.

Recent studies have found the mis-metabolism of a protein, which can affect TDP-43, is correlated to several neurodegenerative diseases, including FTLD and amyotrophic lateral sclerosis (ALS).

In one of the earlier stages of the team's experiments, Tsai's team had transgenically overexpressed TDP-43 in the forebrain of a mouse, successfully producing a lab mouse with phenotypic characteristics similar to FTLD.

Tsai's team used the autophagy activator in the early stages of the mouse's pathology, discovering that they were not only able to maintain the learning ability of the animal, but also slow down the loss of its motor function, as well as reduce the cytosolic overexpression TDP-43 and its abnormal aggregation; therefore ameliorating the proteopathy-induced neuronal apoptosis.

Delivering the autophagy activators at the late stage of the disease progression helps ameliorate motor function, according to Tsai.

The team has also showed that spermidine, carbamazepine and tamoxifen are also autophagy activators like rapamycin, which can also be used to treat FTLD.

Rapamycin treatment has been reported to be beneficial in some animals with neurodegenerative diseases but not others; however, the study shows that rapamycin treatment effectively alleviate learning/memory impairment of mice at 3 months of age; it also significantly slows down the age-dependent loss of their motor function.

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