Title:The Contribution of Proteinase-Activated Receptors to Intracellular Signaling, Transcellular Transport and Autophagy in Alzheimer´s Disease
Volume: 12
Issue: 1
Author(s): Radoslav Matej, Zdenek Rohan, Karel Holada and Tomas Olejar
Affiliation:
Keywords:
Amyloid β, Alzheimer´s disease, autophagy, protein tau, proteinase-activated receptor, reactive oxygen species.
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.
