Mitochondria-Directed Therapies for Alzheimer’s and Parkinson’s Diseases

Written by Quynh Theresa Do and Edited by Kevin Liu

Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are a growing crisis for the United States. Neurodegenerative diseases are diseases that result in the decline of the nervous system’s functionality, especially neuron cells in the brain. Both diseases are large burdens to those afflicted and their caretakers. In particular, Alzheimer’s disease is defined as a progressive neurodegenerative disorder that impacts several areas of cognitive function, including memory. The two hallmarks of Alzheimer’s disease are an accumulation of plaques, specific protein depositions, and tangles, knots of another specific protein. The plaques impede neural connectivity, making it hard for connections to form and reinforce each other in the brain, thereby affecting memory. Tangles cause problems with neuron structure stability, leading to neuron death and subsequent decline of brain health. Parkinson’s disease is another neurodegenerative disorder that affects neurons important for movement. The primary progression of Parkinson’s disease involves the accumulation of alpha-synuclein, a protein that can clump and create toxic blocks in the brain. In both diseases, however, it has been found that mitochondrial dysfunction plays a part in disease progression.

The mitochondria is an essential organelle in the cell that creates ATP, which is used as energy for other parts of the cell to properly function. Mitochondria are also important for other functions such as maintaining proper calcium levels, synthesizing hormones including steroids for growth, and initiating cell death. If the mitochondria does not work properly, this results in a lack of energy for the other organelles in a cell to properly function, which is detrimental to neuron functionality [1]. Mitochondrial dysfunction has been identified as a large part of both Alzheimer’s and Parkinson’s pathologies. Although the mitochondrial aspect of a cell is a non-conventional approach to both diseases’ treatment, as most therapies focus on more well-known and common biomarkers such as protein accumulations, the mitochondria has high potential as a therapy target due to these findings.

Mitochondria-directed therapies have long been applied for mitochondria-related diseases that may cause growth defects and muscular disabilities. For neurodegenerative diseases, mitochondria-directed therapies focus on reducing “oxidative stress” in the brain, which is the brain’s struggle to protect itself against reactive oxygen compounds [2]. These compounds, which are chemically reactive. accelerate the brain aging process. At normal levels, they work alongside and within the mitochondria through biochemical reactions. However, when out of control, they can cause mitochondrial dysfunction and age-mediated changes in brain structure. Essentially, the mitochondria stop working and many changes in brain structure, (e.g. neuron shrinkage) that normally come with age, are initiated. Thus, for both Alzheimer’s and Parkinson’s, antioxidants that target and protect the mitochondria are studied as possible therapies against these reactive oxygen species. For Parkinson’s disease, the herbal medicine found across Asia, Chunghyuldan, was able to prevent the production of these reactive oxygen species and maintain mitochondrial membrane potential, an important chemical balance that allows for the production of energy in a cell [3]. For Alzheimer’s disease, MitoQ, an novel antioxidant supplement, also helped to maintain chemical balances necessary for mitochondrial division, an important aspect in cell proliferation [4]. A focus on the mitochondria is a branched approach that is dependent on the disease being evaluated, yet, there are still concerns of whether the treatments may affect other areas beyond cognitive function, especially since mitochondria play an important role in every cell.

Despite their non-conventional approach, mitochondria-targeted therapies may provide insight on how to treat neurodegenerative diseases. They add a perspective on these diseases that may be overshadowed by their most salient features and widens the spectrum of possible therapies for these diseases to give the field a better understanding of different factors contributing to neurodegeneration and its progression.

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