Neurodegeneration Exploring Commonalities Across Diseases: Workshop Summary (2013) / Chapter Skim
Currently Skimming:
5 Mitochondrial Pathology
5 Mitochondrial Pathology
Pages 45-56
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 45... ...
Because both types of diseases affect multiple pathways and organ systems, they require the approach of systems biology. • Potential therapeutic approaches include medications that induce mitochondrial genesis, catalytic antioxidants to protect against reactive oxygen species, regulators of intracellular cal cium, and regulators of redox potential across mitochondrial membrane.
|
From page 46... ...
Even if mitochondrial defects are not causal, they are likely contributory, noted Neil Kowall of Boston University, and thus any therapy that preserves, enhances, or corrects mitochondrial function is likely to be beneficial in forestalling cell death and disease progression.
|
From page 47... ...
Mitochondrial Dysfunction and Neurodegenerative Diseases As noted above, mitochondrial dysfunction is found in the major neurodegenerative diseases. This section outlines workshop presentations about mitochondrial dysfunction in Parkinson's disease, amyotrophic lateral sclerosis (ALS)
|
From page 48... ...
While he acknowledged that people with early-onset Parkinson's may not benefit from stimulating the pathway because their PINK1 or PARKIN are mutated, people with sporadic Parkinson's disease may benefit, as might others with neurodegenerative disease whose mitochondria are dysfunctional. Amyotrophic Lateral Sclerosis ALS predominantly affects motor neurons, leading to progressive muscle wasting and paralysis.
|
From page 49... ...
Kowall said a great deal of evidence shows that mHTT reduces mitochondrial motility, alters mitochondrial morphology, causes calcium dysregulation, reduces oxidative phosphorylation, and depolarizes the mitochondrial membrane in lymphoblasts of Huntington's disease patients. The depolarization is increased with greater numbers of polyglutamine repeats.
|
From page 50... ...
The finding was later corroborated by others. He asserted that subtle defects in tRNA will generate more global mitochondrial protein synthesis defects.
|
From page 51... ...
He expressed the opinion that "bioenergetics is the common pathophysiological mechanism for all of these neurodegenerative diseases." He was then questioned in the discussion by several skeptical participants who did not agree with his causal attribution. In reply, Wallace described how his team had developed a way to introduce a cytochrome oxidase point mutation in mtDNA and found that the animal developed cardiomyopathy, myopathy, and pathological changes in hippocampal neurons, in retinal ganglion cells, and in the optic nerve.
|
From page 52... ...
Mitochondrial Diseases and Their Utility for Neurodegenerative Disease Given the uncertainty as to what roles mitochondrial dysfunction plays in neurodegerative disease, Mootha suggested the value of studying primary mitochondrial diseases, which refer to nearly 150 genetic diseases in which the lesion lies in a gene encoding a protein that is directly involved in mitochondrial biology. The diseases are heterogeneous, with dozens being the focus of study over many decades.
|
From page 53... ...
Lee Martin of Johns Hopkins University cautioned that cell death in humans versus animal models of neurodegenerative diseases may not be by similar mechanisms. He reported mouse–human species differences in the factors controlling the mitochondrial permeability transition (MPT)
|
From page 54... ...
Regarding therapies, this chapter has already mentioned a few in relation to specific neurodegenerative diseases. Focusing instead on generic therapies for mitochondrial dysfunction, Wallace said his first priority for therapy would be to stimulate formation of more mitochondria.
|
From page 55... ...
(Wallace) • Identify biomarkers to follow mitochondrial functioning.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.