Nucleotides regulate the common molecular mechanisms that underlie neurodegenerative diseases; Therapeutic implications

Abstract

Neurodegenerative diseases (ND) are a heterogeneous group of neurological disorders characterized by a progressive loss of neuronal function which results in neuronal death. Although a specific toxic factor has been identified for each ND, all of them share common pathological molecular mechanisms favouring the disease development. In the final stages of ND, patients become unable to take care of themselves and decline to a total functional incapacitation that leads to their death. Some of the main factors which contribute to the disease progression include proteasomal dysfunction, neuroinflammation, synaptic alterations, protein aggregation, and oxidative stress. Over recent years, evidence has been accumulated to suggest that purinergic signaling plays a key role in the aforementioned molecular pathways. In this review, we revise the implications of the purinergic signaling in the common molecular mechanism underlying the ND. In particular, we focus on the role of the purinergic receptors P2X7, P2Y₂ and the ectoenzyme tissue-nonspecific alkaline phosphatase (TNAP).

Keywords: ATP; Neuroinflammation; Oxidative stress; P2X7R; P2Y2R; Protein aggregation; Spreading; Synaptic dysfunction; TNAP; Ubiquitin proteasome system (UPS).