Purines and Pyrimidines: Metabolism, Function and Potential as Therapeutic Options in Neurodegenerative Diseases

Curr Protein Pept Sci. 2021;22(2):170-189. doi: 10.2174/1389203721999201208200605.

Abstract

Various neurodegenerative disorders have various molecular origins but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.

Keywords: Purines; amyloidosis; neurodegenerative diseases; nucleosides; purinergic signalling; pyrimidines.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloidosis / drug therapy
  • Amyloidosis / enzymology
  • Amyloidosis / genetics
  • Amyloidosis / pathology
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Huntington Disease / drug therapy
  • Huntington Disease / enzymology
  • Huntington Disease / genetics
  • Huntington Disease / pathology
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Hypoxanthine Phosphoribosyltransferase / metabolism
  • Metabolic Networks and Pathways / genetics*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / enzymology
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / pathology
  • Neurofibrillary Tangles / drug effects
  • Neurofibrillary Tangles / enzymology
  • Neurofibrillary Tangles / genetics
  • Neurofibrillary Tangles / pathology
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / pathology
  • Parkinson Disease / drug therapy
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Purines / metabolism
  • Purines / therapeutic use*
  • Pyrimidines / metabolism
  • Pyrimidines / therapeutic use*
  • Synapses / drug effects
  • Thymidine Phosphorylase / genetics
  • Thymidine Phosphorylase / metabolism

Substances

  • Purines
  • Pyrimidines
  • Thymidine Phosphorylase
  • Hypoxanthine Phosphoribosyltransferase
  • Phosphotransferases (Alcohol Group Acceptor)
  • deoxyguanosine kinase
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins