Many of the better known age-related neurodegenerative conditions involve aggregates of damaged or misfolded proteins, but there are other similarities as well. This is too be expected, given that aging is at root caused by a small variety of forms of molecular damage. This damage spirals out into a much larger set of secondary and later consequences, ultimately leading to the wide variety of age-related diseases. Simple processes acting in a complex system, such as human biochemistry, tend to produce complex outcomes. Thus if starting at the point of any two age-related diseases, dig far enough back into their roots and you will arrive at shared origins. Somewhat in that vein, this open access review paper looks over some of the commonalities in Alzheimer’s disease and Parkinson’s disease:
Alzheimer’s disease and Parkinson’s disease are two common neurodegenerative diseases of the elderly people that have devastating effects in terms of morbidity and mortality. The predominant form of the disease in either case is sporadic with uncertain etiology. The clinical features of Parkinson’s disease are primarily motor deficits, while the patients of Alzheimer’s disease present with dementia and cognitive impairment. Though neuronal death is a common element in both the disorders, the postmortem histopathology of the brain is very characteristic in each case and different from each other. In terms of molecular pathogenesis, however, both the diseases have a significant commonality, and proteinopathy (abnormal accumulation of misfolded proteins), mitochondrial dysfunction and oxidative stress are the cardinal features in either case.
These three damage mechanisms work in concert, reinforcing each other to drive the pathology in the aging brain for both the diseases; very interestingly, the nature of interactions among these three damage mechanisms is very similar in both the diseases. In the case of Alzheimer’s disease, the peptide amyloid beta (Aβ) is responsible for the proteinopathy, while α-synuclein plays a similar role in Parkinson’s disease. The expression levels of these two proteins and their aggregation processes are modulated by reactive oxygen radicals and transition metal ions in a similar manner. In turn, these proteins – as oligomers or in aggregated forms – cause mitochondrial impairment by apparently following similar mechanisms. Understanding the common nature of these interactions may, therefore, help us to identify putative neuroprotective strategies that would be beneficial in both the clinical conditions.