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The Contribution of Proteinase-Activated Receptors to Intracellular Signaling, Transcellular Transport and Autophagy in Alzheimer´s Disease

[ Vol. 12 , Issue. 1 ]

Author(s):

Radoslav Mat ej, Zden ek Rohan, Karel Holada and Tomas Olejar   Pages 2 - 12 ( 11 )

Abstract:


The etiopathogenesis of Alzheimer´s disease is characterized by beta amyloid Aβ(1-42) toxic fragment aggregation and its association with impaired autophagy. In mitochondria, chronic damage due to transport and enzymatic processes together with the production of reactive oxygen species (ROS) are followed by the subsequent accumulation of Aβ in the form of senile plaques and the accumulation of hyperphosphorylated tau protein in intracellular deposits called tangles. Proteinase-activated receptors (PARs), members of the G protein-coupled receptor (GPCR) family, facilitate and modulate the transcellular transport and distribution of a variety of subcellular molecular components to the lysosomal system and, thus, influence their degradation. A review of the data shows that the activation or inhibition of PARs leads to changes in the process of autophagy, which may influence ROS production and Aβ (1-42) degradation in lysosomes and result in AD pathogenesis.

Keywords:

Amyloid β, Alzheimer´s disease, autophagy, protein tau, proteinase-activated receptor, reactive oxygen species.

Affiliation:

Department of Membrane Transport Biophysics, No. 75, Institute of Physiology, Academy of Sciences, 142 20 Prague, Czech Republic.



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