title: Re-expression of cell cycle markers in aged neurons and muscles: Whether cells should divide or die?
abstract: Emerging evidence revealed that abrogated cell cycle entry into highly differentiated mature neurons and muscles is having detrimental consequences in response to cell cycle checkpoints disruption, altered signaling cascades, pathophysiological and external stimuli, for instance, Aβ, Parkin, p-tau, α-synuclein, impairment in TRK, Akt/GSK3β, MAPK/Hsp90, and oxidative stress. These factors, reinitiate undesired cell division by triggering new DNA synthesis, replication, and thus exquisitely forced mature cell to enter into a disturbed and vulnerable state that often leads to death as reported in many neuro- and myodegenerative disorders. A pertinent question arises how to reverse this unwanted pathophysiological phenomenon is attributed to the usage of cell cycle inhibitors to prevent the degradation of crucial cell cycle arresting proteins, cyclin inhibitors, chaperones and E3 ligases. Herein, we identified the major culprits behind the forceful cell cycle re-entry, elucidated the cyclin re-expression based on disturbed signaling mechanisms in neuromuscular degeneration together with plausible therapeutic strategies.
authors.affiliation: Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042, India.
authors.forename: Niraj Kumar
authors.initials: NK
authors.lastname: Jha
authors.affiliation: Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042, India.
authors.forename: Saurabh Kumar
authors.initials: SK
authors.lastname: Jha
authors.affiliation: Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042, India.
authors.forename: Rashmi K
authors.initials: RK
authors.lastname: Ambasta
authors.affiliation: Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042, India. Electronic address: pravirkumar@dce.edu.
authors.forename: Pravir
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000375:Aging; D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division; D018844:Cyclin-Dependent Kinases / Q000032:analysis* / Q000378:metabolism; D016213:Cyclins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D009132:Muscles / Q000166:cytology / Q000473:pathology*; D009468:Neuromuscular Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000473:pathology*; D013312:Stress, Physiological
chemical_list: D016213:Cyclins; D018844:Cyclin-Dependent Kinases
keywords: Cyclins; Neuromuscular degeneration; Post-mitotic cell division; Signaling cascade; Therapeutics