ISCTM 7th Annual Scientific Meeting – Mitochondrial Systems Working Group Dinner – Summary
Working Group Dinner
21 Feb 2011
Chair: C Bowden
Several recently published examples of mitochondrial dysfunction in brain, particularly in diminished oxidative metabolism to supply energy to brain neurons, were provided by ISCTM members involved in this work group. In the aggregate, the data support the hypothesis that mitochondrial dysfunction can be causal of primary observable disease, rather than fundamentally consequent to other primary disease processes. For example, children of diabetics displayed significant reductions in size of mitochondria compared to controls, raising the possibility that insulin resistance could serve as one biomarker of mitochondrial dysfunction. Similarly, a microarray study of cortical tissue in Alzheimer Disease, in press in Molecular Psychiatry, co –authored by Terry Goldberg, implicates genes operational in mitochondria,
Disturbances in systems biology and evidence of genetic disturbances are likely to be causally contributory to a variety of severe, chronic psychiatric and neurological disorders, classical mitochondrial disorders, and, possibly, milder forms of cognitive impairment. Consequently, directing new drug developments toward mitochondrial systems, as well as the upstream inputs that either facilitate mitochondrial resilience or adversely impact mitochondrial functions is a promising strategy . Two relevant examples are BDNF and Bcl-2. Valproate and other histone deacetylase inhibitors (HDAC) increase BDNF, and consequently promote survival of dopaminergic neurons. Bcl-2 is protective against many adverse endogenous and exogenous insults (stroke, elevated glutamate, ß amyloid, methamphetamine. Lithium, via GSK-3 inhbition, protects Bcl-2 against degradation from such insults.
Workgroup participants agree that a straightforward review of mitochondrial function, emphasizing those aspects directly relevant to CNS function, could serve to inform a wide range of scientists working in related clinical and basic areas of CNS diseases. We see several aspects of mitochondrial systems that are amenable to potential drug development and other non-drug interventions.
Relatedly, several features of mitochondrial function, possibly interlinked with genomic data, appear suitable for treatment as biomarkers both for diagnosis and treatment selection.
ISCTM members desiring to join this workgroup, or who have relevant information for our collating efforts are encouraged to contact Dr. Bowden.