title: Protein N-homocysteinylation: From cellular toxicity to neurodegeneration.
abstract: BACKGROUND
  Homocysteine (Hcy) is a sulfur containing non-protein amino acid that occupies a central role in metabolism of thiol compounds. The past decade had noticed an explosion in interests of Hcy and this very interest came primarily from the fact that increased Hcy level is related to various neurodegenerative and vascular complications.
  
  
  METHODS
  Several factors responsible for the Hcy-associated neurotoxicity have been proposed and well documented in literature, including oxidative stress and apoptosis. In addition, protein covalent modification by the metabolite of Hcy, Hcy thiolactone (HTL), has now been shown to be another cause of cellular Hcy toxicity. This mechanism, termed as "protein N-homocysteinylation", is known to result in protein denaturation, enzyme inactivation and even amyloid formation. The role of protein N-homocysteinylation and the resulting consequences with regard to neurodegeneration have not yet been extensively discussed. The present review describes major advances in understanding protein N-homocysteinylation and their role in neurodegeneration.
  
  
  CONCLUSIONS
  Formation of protein aggregates/amyloids are crucial events in various human pathologies including neurodegenerative diseases. Since elevated Hcy has been closely linked to neurodegeneration, N-homocysteinylation-induced protein modification and aggregates/amyloids formation could be one possible mechanism for the neurodegenerative conditions.
  
  
  CONCLUSIONS
  The information highlighted here provides us an understanding of the role protein modification by N-homocysteinylation in neurodegenerative diseases.
authors: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors: Gurumayum Suraj
authors: GS
authors: Sharma
authors: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors: Tarun
authors: T
authors: Kumar
authors: Department of Clinical Biochemistry, University of Kashmir, Jammu & Kashmir, India.
authors: Tanveer Ali
authors: TA
authors: Dar
authors: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India. Electronic address: lairksingh@gmail.com.
authors: Laishram Rajendrakumar
authors: LR
authors: Singh
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology; D000682:Amyloid / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D006710:Homocysteine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology*; D009474:Neurons / Q000187:drug effects*; D011328:Prions / Q000378:metabolism; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D011328:Prions; D066329:Protein Aggregates; D006710:Homocysteine; C007957:homocysteine thiolactone
keywords: Amyloids; Homocysteine; Homocysteine thiolactone; Homocystinuria; Neurodegenerative disease; Protein N-homocysteinylation