The most prevalent of NDDs includes Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), spinocerebellar ataxias (SCA), prion diseases (PrD) and others.
Neurodegenerative diseases (NDDs) are becoming increasingly prevalent in an age-dependent manner, partly because life expectancy has increased in recent years due to our advanced medical knowledge.
In this review, while acknowledging the hallmark proteins which characterize the most common NDDs we place specific focus on the common overlapping mechanisms leading to disease pathology despite these different molecular players and discuss how this convergence may occur, with the ultimate hope that therapies effective in one disease may successfully translate to another. Damage within these neurons is enhanced by damage from the nonneuronal cells, via inflammatory processes that accelerate the progression of these diseases. These pathological proteins, which characterize each specific disease, lead to the selective vulnerability of different neurons, likely resulting from a combination of different intracellular mechanisms, including mitochondrial dysfunction, ER stress, proteasome inhibition, excitotoxicity, oxidative damage, defects in nucleocytoplasmic transport, defective axonal transport and neuroinflammation.
These large inclusions, most likely, represent an end stage of a molecular cascade however, the soluble misfolded proteins, which take part in earlier steps of this cascade, are the more toxic players. Multiple neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD) are being suggested to have common cellular and molecular pathological mechanisms, characterized mainly by protein misfolding and aggregation.
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