Unraveling the Role of Cell Death in Neurodegeneration
The principal research focus of Dr. Daniel Linseman's laboratory is to elucidate the molecular mechanisms by which neurons die in various neurodegenerative disorders. A major emphasis is to understand the role of mitochondrial oxidative stress and intrinsic apoptosis (programmed cell death) in neurodegeneration. Specific projects that are currently ongoing in the laboratory include: 1) identification of novel pathways by which pro-survival Bcl-2 proteins (eg., Bcl-2 and Mcl-1) protect neurons from mitochondrial oxidative stress and apoptosis; 2) determination of the mechanisms by which pro-death Bcl-2 proteins (eg., Bim and Puma) trigger mitochondrial oxidative stress and apoptosis; and 3) evaluation of natural product polyphenolic antioxidants (eg., green tea EGCG and red grape resveratrol) for their neuroprotective effects against mitochondrial oxidative stress and neuronal apoptosis. The laboratory routinely utilizes primary cultures of neurons obtained from rat cerebellum as an in vitro model to investigate neuronal apoptosis. The laboratory also employs mouse models of Parkinson's disease and amyotrophic lateral sclerosis to study neuronal apoptosis in vivo. Ultimately, Dr. Linseman hopes to identify novel regulators of mitochondrial oxidative stress and intrinsic apoptosis that can be targeted to limit neuronal loss and slow the progression of various neurodegenerative diseases.