TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer's disease.

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD's main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca-dependent proteins transamidation, including the Aβ peptide.

Increased P2×2 receptors induced by amyloid-β peptide participates in the neurotoxicity in alzheimer's disease.

Amyloid beta peptide (Aβ) is tightly associated with the physiopathology of Alzheimer's Disease (AD) as one of the most important factors in the evolution of the pathology. In this context, we previously reported that Aβ increases the expression of ionotropic purinergic receptor 2 (P2×2R). However, its role on the cellular and molecular Aβ toxicity is unknown, especially in human brain of AD patients.