Therapeutic Value of Mitochondrial Support for Neurodegenerative Disorders

by aiP / 2016


Table of Contents



This small sample of abstracts, articles and talks was compiled for the attention of Patient X's consultant following a meeting (in April 2016) between the consultant and the author of this compilation.

See: Mitochondria, Statins and Parkinson-like Symptoms for background and context.



Does supporting mitochondrial function have therapeutic value for people with Parkinson's?

Mitochondrial Dysfunction in Parkinson's Disease (2009, Abstract)

Konstanze F. Winklhofer, Christian Haass doi:10.1016/j.bbadis.2009.08.013

Mitochondria are highly dynamic organelles which fulfill a plethora of functions. In addition to their prominent role in energy metabolism, mitochondria are intimately involved in various key cellular processes, such as the regulation of calcium homeostasis, stress response and cell death pathways. Thus, it is not surprising that an impairment of mitochondrial function results in cellular damage and is linked to aging and neurodegeneration. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD), starting in the early 1980s with the observation that an inhibitor of complex I of the electron transport chain can induce parkinsonism. Remarkably, recent research indicated that several PD-associated genes interface with pathways regulating mitochondrial function, morphology, and dynamics. In fact, sporadic and familial PD seem to converge at the level of mitochondrial integrity.



The Parkinson Disease Mitochondrial Hypothesis (2015, Abstract)

Celine Perier, Neurodegenerative Diseases Research Group

Parkinson’s disease is a common, adult-onset neurodegenerative disorder whose pathogenesis is still under intense investigation. Substantial evidence from postmortem human brain tissue, genetic- and toxin-induced animal and cellular models indicates that mitochondrial dysfunction plays a central role in the pathophysiology of the disease. This review discusses our current understanding of Parkinson’s disease–related mitochondrial dysfunction, including bioenergetic defects, mitochondrial DNA alterations, altered mitochondrial dynamics, activation of mitochondrial-dependent programmed cell death, and perturbations in mitochondrial tethering to the endoplasmic reticulum. Whether a primary or secondary event, mitochondrial dysfunction holds promise as a potential therapeutic target to halt the progression of neurodegeneration in Parkinson’s disease.



MicroRNA-7 Regulates the Function of Mitochondrial Permeability Transition Pore by Targeting VDAC1 Expression (2015, rev. 2016, Abstract)

Amrita Datta Chaudhuri, Doo Chul Choi, Savan Kabaria, Alan Tran and Eunsung Junn Dept. of Neurology, Rutgers – Robert Wood Johnson Medical School

Mitochondrial dysfunction is one of the major contributors to neurodegenerative disorders including Parkinson disease. The mitochondrial permeability transition pore is a protein complex located on the mitochondrial membrane. Under cellular stress, the pore opens, increasing the release of pro-apoptotic proteins, and ultimately resulting in cell death. MicroRNA-7 (miR-7) is a small non-coding RNA that has been found to exhibit a protective role in the cellular models of Parkinson disease. In the present study, miR-7 was predicted to regulate the function of mitochondria, according to gene ontology analysis of proteins that are down-regulated by miR-7. Indeed, miR-7 overexpression inhibited mitochondrial fragmentation, mitochondrial depolarization, cytochrome c release, reactive oxygen species generation, and release of mitochondrial calcium in response to 1-methyl-4-phenylpyridinium (MPP+) in human neuroblastoma SH-SY5Y cells. In addition, several of these findings were confirmed in mouse primary neurons. Among the mitochondrial proteins identified by gene ontology analysis, the expression of voltage-dependent anion channel 1 (VDAC1), a constituent of the mitochondrial permeability transition pore, was down-regulated by miR-7 through targeting 3'-untranslated region of VDAC1 mRNA. Similar to miR-7 overexpression, knockdown of VDAC1 also led to a decrease in intracellular reactive oxygen species generation and subsequent cellular protection against MPP+. Notably, overexpression of VDAC1 without the 3'-UTR significantly abolished the protective effects of miR-7 against MPP+-induced cytotoxicity and mitochondrial dysfunction, suggesting that the protective effect of miR-7 is partly exerted through promoting mitochondrial function by targeting VDAC1 expression. These findings point to a novel mechanism by which miR-7 accomplishes neuroprotection by improving mitochondrial health.



A Mitochondrial Etiology of Metabolic and Degenerative Diseases & Cancer

Douglas Wallace, Perelman School of Medicine at the University of Pennsylvania



Protein Folding and Rescuing Neurons

Susan Lindquist Keynote Lecture at The International Society for Stem Cell Research in Vancouver, 2014




Dietary protocols and lifestyle interventions for upregulating mitochondrial function, gene expression etc.

Some promising recent research into effective therapies for: MND (i.e. ALS), Alzheimer's, Parkinson's & Cancer

Dr. D'Agostino is an Assistant Professor at the University of South Florida College Of Medicine, Molecular Pharmacology & Physiology where he develops and tests metabolic therapies for neurological disorders, cancer and wound healing.


MCT / Coconut Oil Study

A Randomized, Double-Blind, Placebo-Controlled, 6 Month Cross-Over Study to Evaluate the Efficacy of Coconut Oil Treatment for Subjects With Mild to Moderate Alzheimer's Disease

Article: Prevention is the best way of tackling Alzheimer’s. So why is it being ignored and discredited?

[Excerpt]  So I make no apology for writing again about what happened to the Oxford professor of Pharmacology who ran a very proper trial showing that high dose B vitamins could reduce shrinkage in areas of the brain specifically involved in Alzheimer’s by 90%. [Read on ...]

Nutrigenomics, Epigenetics, and Stress Tolerance

An interesting talk on protein misfolding, Foxo3, HSPs, and the effect of diet on gene expression and repair (for a non-technical lay audience, but relevant). Dr Patrick earned her Ph.D. in biomedical science from the University of Tennessee. She has done extensive research on aging, cancer and nutrition, and metabolism.




Evidence Based Medicine

How Credible are Current Trials & Studies?

Richard Horton (The Lancet, Vol 385 April 11, 2015)

The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness. As one participant put it, “poor methods get results”. The Academy of Medical Sciences, Medical Research Council, and Biotechnology and Biological Sciences Research Council have now put their reputational weight behind an investigation into these questionable research practices.



Article: Evidence based medicine doesn’t protect patients – it just prevents them getting unpatentable treatments

[Excerpt]  For years we have been assured that medical treatments are approved on the basis of evidence gathered impartially from research and clinical trials. This is evidence based medicine and without its approval any treatment is dismissed as probably worthless and possibly dangerous.

It’s now very clear, however, these trials can be highly unreliable and partial. [...] What we actually have is commercially based medicine.  [Read on ...]


I've included the following talk in part to highlight the frustrations (see: suffered by academics when they are highlighting serious problems with existing paradigms and recommending the studying/trialling of well researched alternatives.

Targeting Energy Metabolism in Brain Cancer (The barriers to non-pharmaceutical trials)

Dr Thomas Seyfried is Professor of Biology at Boston College whose research involves gene-environmental interactions in neurological and neurodegenerative diseases including epilepsy, autism, gangliosidoses, and brain cancer.




Do Statin's increase the risk of Parkinson's?

Statins lower your body’s levels of coenzyme Q10. As your CoQ10 levels go down so does mitochondrial ATP production, while free radical formation increases. Since the link between mitochondrial function and Parkinson's is well established, as is the connection between free radical damage, it's hard to see how statins cannot increase the risk Parkinson's.

Long Term US epidemiological study

The Atherosclerosis Risk in Communities Study. An ongoing 20 year epidemiological study covering the decade before and the decade following the introduction of statins.

Parkinson's findings:

US researchers looked at blood cholesterol levels, medications and Parkinson’s disease status in nearly 16,000 men and women who participated in the ongoing, long-term Atherosclerosis Risk in Communities study. During the study, the researchers took cholesterol readings at three-year intervals over the course of a decade from 1987 to 1998, before widespread statin use began. Then, from 1998 to 2008, they tracked how many men and women had started statin therapy, and how many of them developed Parkinson’s disease.

The results showed that men and women who took statin drugs were twice as likely to develop Parkinson’s disease. But here’s the interesting part: The researchers linked higher total cholesterol with lower Parkinson’s disease risk.

NOTE: Certainly there are UK studies (Government and Parkinson's NGO) that show Parkinson's as either flat (decreasing in some age groups and increasing in others) or increasing with statistical trend-based caveats. Those same studies generally show a substantial increase for Alzheimer's.



Article: Companies clash over statin side effects. Which is lying? (2016)

[Excerpt]  This presented a problem for the plan to market Repatha as free of serious muscle pain risk, which they claim comes with statins. If the statin pain is not “real” you don’t need a very expensive drug to avoid it. This was why the finding that 42.6% of patients given a statin had reported serious muscle pains, many fewer than those getting a placebo, was so important. [...] What this trial of Repatha did was actually to test patient’s claims of muscle pains, rather than dismiss them as doctors have commonly done.

This was something that could have been done at any time in the last two decades but never was for obvious commercial reasons. Should we really have to wait for the launch of a new drug before we even have a chance of finding out the truth about an existing one?  [Read on ...]