Ajou Medical University Professor Jaerak Jang’s team published a paper in the international journal ‘Autophagy’
Autophagy regulator ‘TRIM22 protein’ discovered… Expectations for the development of new treatments
TRIM22 mutation → reduced autophagy activity → accumulation of neurotoxic substances
Professor Jang Jae-rak of Ajou Medical University (left) and graduate student Heo Han-sol.
A new molecular pathogenesis of Alzheimer’s disease, a representative neurodegenerative disease that causes dementia, has been revealed.
Professor Jang Jae-rak’s team at Ajou Medical University (Department of Neuroscience, first author Heo Han-sol graduate student) newly discovered ‘TRIM22 protein’ as a regulator of autophagy, an essential mechanism for maintaining intracellular protein homeostasis, and identified its mechanism of action. .
According to an existing study conducted on Alzheimer’s disease patients with PSEN-1 mutation, the highest genetic factor causing familial Alzheimer’s disease, ‘TRIM22-R321K mutation’ has a very high genetic risk of hastening the onset of Alzheimer’s disease. It’s a factor. Familial Alzheimer’s disease is a form of Alzheimer’s disease caused by mutations in specific genes, and is characterized by the onset of dementia symptoms at a relatively early age.
Autophagy, a process in which cells decompose unnecessary substances on their own, is an essential mechanism for maintaining intracellular protein homeostasis, and various neurodegenerative diseases, including Alzheimer’s disease, are closely related to abnormal autophagy activity.
Intracellular wastes surrounded by organelles called autophagosomes are decomposed through fusion with lysosomes containing decomposition enzymes.
The research team demonstrated that the TRIM22 protein regulates efficient intracellular decomposition activity by mediating the fusion of the two organelles through binding to the GABARAPs protein present in the autophagosome and the PLEKHAM1 protein present in the lysosome.
In addition, they proposed a new molecular pathogenesis of Alzheimer’s disease by demonstrating that the TRIM22 function is inhibited by the TRIM22-R321K mutation, resulting in decreased autophagy activity and accumulation of neurotoxic substances.
Professor Jae-Rak Jang said, “Recently, the field of Alzheimer’s disease has been making remarkable progress in terms of research along with the approval of new treatments, but understanding of the fundamental pathogenic mechanism is still lacking. This study will be used as the basis for developing a new treatment for Alzheimer’s disease.” “I hope so,” he said.
This study was published in a renowned international journal in the field of cell biology.
This study was supported by the Ministry of Science and ICT’s Mid-career Researcher Support Project and the Leading Research Center (MRC, Brain Disease Convergence Research Center) and was conducted in collaboration with Professor Lee Seong-joo’s team at Inha University Medical School.
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2023-12-27 04:58:55
#molecular #pathogenesis #Alzheimers #disease #identified.. #Autophagy #key
