Andrey Tsvetkov
Assistant Professor
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Neurology
Huntington’s disease is caused by the abnormal expansion of a polyglutamine stretch in the huntingtin protein. The polyglutamine expansion is associated with huntingtin accumulation and aggregation into inclusion bodies. Accumulation of mutant huntingtin in neurons suggests that mechanism of its degradation is altered.
There are two primary mechanisms by which cells turn over cellular content. The ubiquitin-proteasome system degrades normal monomeric proteins and polypeptides. The second pathway, autophagy, directs proteins and organelles to lysosomes. There are three different types of autophagy: chaperone-mediated autophagy (CMA), macroautophagy, microautophagy. CMA mediates only degradation of soluble proteins. Single protein molecules are recognized by a specific cytosolic chaperone and a receptor on the lysosomal membrane, which then facilitate translocation of the protein into the lysosomal lumen. On induction of macroautophagy, cytoplasmic content or an organelle is sequestered inside double-membrane vesicles called autophagosomes. The autophagosomes subsequently fuse to the lysosomes for degradation and recycling. In microautophagy, cytosolic content can be sequestered directly by direct invagination of the lysosomal membrane. My research focuses on the physiological and pathophysiological functions of macroautophagy in age-associated neuronal dysfunction and neurodegeneration such as Huntington’s disease. Our studies strongly suggest that at least some autophagic pathways can be modified with autophagy enhancers to boost degradation of abnormal protein, resulting in improved neuronal health. The ability of autophagy enhancers to increase removal of toxic material suggests that age-associated neurodegeneration can be halted or even reversed.
In the lab we use multiple approaches, including molecular, cell, and chemical biology, and unique microscopy techniques to understand molecular mechanisms of neuronal autophagy.
McGovern Medical School Faculty
Education & Training
Ph.D. - University of Illinois, Chicago - 2005