A southern Taiwan-based National Cheng Kung University (NCKU) research
team has discovered that rapamycin, a drug as a autophagy activator is a
possible treatment to alleviating frontotemporal lobar degeneration
(FTLD), one of the mainly causes of dementia, and so far no medication
can be used.
The medical breakthrough made by the team led by Kuen-Jer Tsai,
professor of 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
To activate autophagy, the process of self-digestion by a cell, is the
crucial discovery of the research, according to Tsai adding that
autophagy activators rescue and alleviate pathogensis of a mouse model
with protein pathies of the TAR DNA-binding protein 43 (TDP-43), a
neuronal activity, which is the main syndrome of FTLD.
"The pathological and clinical syndrome of FTLD including the brain
atrophy of frontal and temporal lobe, memory loss, speechless,
neuromotor disorders, even would be complicating with motor neuron
disease," said Kuen-Jer Tsai.
In the elderly population over the age of 65, FTLD is the fourth most
common reasons of dementia, only after Alzheimer's disease, Lewy body
dementia and vascular dementia.
However, FTLD is the second common reasons of dementia just next to
Alzheimer's disease in the populations 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 the earlier stage, Kuen-Jer Tsai's team had transgenically
overexpressed TDP-43 in the forebrain of a mouse, successfully
development an animal model existing phenotypic characteristics
mimicking of FTLD.
Tsai's team applied the animal models give autophagy activator in the
early stage of pathology, discovering that not only maintaining the
learning/memory ability of the animal model but also slow down the loss
the motor function, and reducing cytosolic overexpression TDP-43 and its
abnormally aggregation, therefore ameliorating the proteinopathy-induced
Delivering the autophagy activators at the late stage of disease
progression can ameliorate the motor function, according to Tsai.
The team has also showed that spermidine, carbamazepine, and tamoxifen
are autophagy activators like rapamycin could also be used to the
treatment of FTLD.
National Cheng Kung University