The Neuronal Kinesin UNC-104/KIF1A Is a Key Regulator of Synaptic Aging and Insulin Signaling-Regulated Memory

Current Biology : CB
Ling-Bo LiKang Shen

Abstract

Aging is the greatest risk factor for a number of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Furthermore, normal aging is associated with a decline in sensory, motor, and cognitive functions. Emerging evidence suggests that synapse alterations, rather than neuronal cell death, are the causes of neuronal dysfunctions in normal aging and in early stages of neurodegenerative diseases. However, little is known about the mechanisms underlying age-related synaptic decline. Here, we uncover a surprising role of the anterograde molecular motor UNC-104/KIF1A as a key regulator of neural circuit deterioration in aging C. elegans. Through analyses of synapse protein localization, synaptic transmission, and animal behaviors, we find that reduced function of UNC-104 accelerates motor circuit dysfunction with age, whereas upregulation of UNC-104 significantly improves motor function at advanced ages and also mildly extends lifespan. In addition, UNC-104-overexpressing animals outperform wild-type controls in associative learning and memory tests. Further genetic analyses suggest that UNC-104 functions downstream of the DAF-2-signaling pathway and is regulated by the FOXO transcription factor DAF-16, which contri...Continue Reading

References

Dec 2, 1993·Nature·C KenyonR Tabtiang
Nov 19, 2003·Neuron·Patrik VerstrekenHugo J Bellen
Nov 19, 2003·Neuron·Kimberly R SchuskeErik M Jorgensen
Jun 11, 2004·Nature·Tao LuBruce A Yankner
Feb 26, 2005·Science·Gorazd B StokinLawrence S B Goldstein
Jul 29, 2005·Nature·Derek SieburthJoshua M Kaplan
Aug 29, 2006·Experimental Gerontology·Coleen T Murphy
Jul 24, 2007·Nature Neuroscience·Eunju Pack-ChungThomas L Schwarz
Mar 11, 2008·Neuroscience·A PetersJ I Luebke
Oct 31, 2008·PLoS Biology·Laurent KappelerMartin Holzenberger
Jun 4, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dani DumitriuJohn H Morrison
Jun 5, 2010·PLoS Genetics·Matthew A SchreiberSteven L McIntire
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gregorio ValdezJoshua R Sanes
May 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Chun-Liang PanSteven McIntire
Jun 24, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elizabeth M H TankCynthia Kenyon
Mar 8, 2012·Nature Reviews. Neuroscience·John H Morrison, Mark G Baxter
Jun 30, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marton Lorant TothMonica Driscoll
Jul 17, 2012·Neuron·Thomas C Südhof
Jan 25, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cyril BoriesYves De Koninck
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Jun 26, 2013·Cell·Rebecca C Taylor, Andrew Dillin
Jul 16, 2014·Cell Metabolism·Kevin W WilliamsJoel K Elmquist
Aug 5, 2014·Nature Neuroscience·Melanie A SamuelJoshua R Sanes
Aug 12, 2014·Neurobiology of Learning and Memory·Geneva M Stein, Coleen T Murphy

❮ Previous
Next ❯

Citations

Jun 23, 2016·Behavioural Brain Research·Rachel N Arey, Coleen T Murphy
Aug 10, 2016·The Journal of Cell Biology·Colleen N McLaughlinHeather T Broihier
Aug 30, 2016·Experimental Neurology·Alexandra B Byrne, Marc Hammarlund
Nov 16, 2017·Wiley Interdisciplinary Reviews. Developmental Biology·Evguenia IvakhnitskaiaChieh Chang
Jan 5, 2020·Molecular Neurobiology·Jonathan Chang-Cheng ShiehYung-Feng Lin
Sep 27, 2019·Frontiers in Cellular Neuroscience·Francesca Mattedi, Alessio Vagnoni
Jan 1, 2020·Scientific Reports·Rachel N AreyColeen T Murphy
Oct 9, 2020·Journal of Neurogenetics·Amruta Vasudevan, Sandhya P Koushika
Apr 27, 2020·The FEBS Journal·Doryaneh AhmadpourThomas Nystrom
Jun 4, 2020·Ageing Research Reviews·Sophie VanhunselLieve Moons
Nov 6, 2017·Trends in Genetics : TIG·Colleen N McLaughlin, Heather T Broihier

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.