Alexander Yakovlev, Ph. Major directions of my studies center on the regulatory mechanisms of protein and DNA degradation during neuronal degeneration. Our recent experiments established a role of Caspase 3 in neuronal apoptosis in vivo and in vitro and suggested that blockade of this caspase leads to reduction of cell death and associated neurological dysfunction. Currently we are elucidating mechanisms responsible for the regulation of caspase-3 gene activity.
Genome degradation is an established biochemical marker of apoptosis.
We have identified a chromatin-bound CME that has been previously assigned as DNAS1L3. DNA degradation catalyzed by DNAS1L3 contributes essentially to apoptotic process, it has a significant effect on cell viability, and that regulation of this endonuclease must have functional consequences for control of programmed cell death. Accordingly, our studies may provide the basis for new therapeutic strategies for the treatment of acute CNS injuries and chronic degenerative conditions, where the essential role of apoptosis has been established. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. Role of PARP cleavage in apoptosis.