title: Silencing of CDK5 as potential therapy for Alzheimer's disease.
abstract: Neurodegeneration is one of the greatest public health challenges for the 21st century. Among neurodegenerative diseases, Alzheimer's disease (AD) is the most prevalent and best characterized. Nevertheless, despite the large investment in AD research, currently there is no effective therapeutic option. In the present review, we highlight a novel alternative, which takes advantage of the biotechnological outbreak deployed by the discovery of the RNA interference-based gene silencing mechanism, and its application as a tool for neurodegeneration treatment. Here, we highlight cyclin-dependent kinase 5 (CDK5) as a key candidate target for therapeutic gene silencing. Unlike other members of the cyclin-dependent kinase family, CDK5 does not seem to play a crucial role in cell cycle regulation. By contrast, CDK5 participates in multiple functions during nervous system development and has been established as a key mediator of Tau hyperphosphorylation and neurofibrillary pathology, thus serving as an optimal candidate for targeted therapy in the adult nervous system. We propose that the use of RNA interference for CDK5 silencing presents an attractive and specific therapeutic alternative for AD and perhaps against other tauopathies.
authors.affiliation: Cellular and Molecular Neurobiology Area, Viral Vector Core and Gene Therapy, Group of Neuroscience of Antioquia, Faculty of Medicine, SIU, University of Antioquia, Medellin, Colombia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Tobón
authors.forename: John Fredy
authors.initials: JF
authors.lastname: Castro-Álvarez
authors.forename: Diego
authors.initials: D
authors.lastname: Piedrahita
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Boudreau
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gallego-Gómez
authors.forename: Gloria Patricia
authors.initials: GP
authors.lastname: Cardona-Gómez
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000628:therapy*; D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000201:enzymology; D010766:Phosphorylation; D034622:RNA Interference / Q000502:physiology*
chemical_list: D051360:Cyclin-Dependent Kinase 5