Abstract

Neurodegenerative diseases are one of the most important medical and social problems affecting elderly people, the percentage of which is significantly increasing in the total world population. The cause of these diseases is the destruction of neurons by protein aggregates that form pathological deposits in neurons, glial cells and in the intercellular space. Proteins whose molecules are easily destabilized by point mutations or endogenous processes are alpha-synuclein (ASN), tau and TDP-43. Pathological forms of these proteins form characteristic aggregates, which accumulate in the neurons and are the cause of various forms of dementia and motor disorders. The most common causes of dementia are tauopathies. In primary tauopathies, which include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick’s disease (PiD), and frontotemporal dementia (FTD), modified tau molecules disrupt axonal transport and protein distribution in neurons. Ultimately, the helical filaments and neurofibrillary tangles of tau lead to neuron death in various structures of the brain. In Alzheimer’s disease hyperphosphorylated tau tangles along with β amyloid plaques are responsible for the degeneration of the hippocampus, entorhinal cortex and amygdala. The most prevalent synucleinopathies are Parkinson’s disease, multiple system atrophy (MSA) and dementia with Lewy bodies, where there is a degeneration of neurons in the extrapyramidal tracts or, as in MSA, autonomic nerves. TDP-43 inclusions in the cytoplasm cause the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) and in one of the frontotemporal dementia variant (FTLD-TDP). In this work ASN, tau and TDP-43 structures are described, as well as the genetic and sporadic factors that lead to the destabilization of molecules, their aggregation and incorrect distribution in neurons, which are the causes of neurodegenerative diseases.

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