Proteasomal and autophagic degradative activities in spinal and bulbar muscular atrophy.

Neurobiology of Disease
Paola RusminiA Poletti

Abstract

Spinal and bulbar muscular atrophy (SBMA or Kennedy's disease) is a fatal neurodegenerative disease characterized by the selective loss of motor neurons in the bulbar region of the brain and in the anterior horns of the spinal cord. The disease has been associated to an expansion of a CAG triplet repeat present in the first coding exon of the androgen receptor (AR) gene. SBMA was the first identified member of a large class of neurodegenerative diseases now known as CAG-related diseases, which includes Huntington's disease (HD), several types of spinocerebellar ataxia (SCAs), and dentatorubral and pallidoluysian atrophy (DRPLA). The expanded CAG tract is translated to an aberrantly long polyglutamine tract (ARpolyQ) in the N-terminal region of the AR protein. The elongated polyQ tract seems to confer a neurotoxic gain-of-function to the mutant AR, possibly via the generation of aberrant conformations (misfolding). Protein misfolding is thought to be a trigger of neurotoxicity, since it perturbs a wide variety of motor neuronal functions. The first event is the accumulation of the ARpolyQ into ubiquitinated aggregates in a ligand (testosterone) dependent manner. The mutant ARpolyQ also impairs proteasome functions. The autophagi...Continue Reading

References

Feb 1, 1989·Brain : a Journal of Neurology·G SobueA Takahashi
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·M F PerutzJ T Finch
Jun 15, 1993·Journal of Neuroscience Research·K A KujawaK J Jones
Oct 1, 1995·Trends in Neurosciences·B P Brooks, K H Fischbeck
Jan 1, 1997·Brain Research Bulletin·A Matsumoto
Jun 10, 1998·Steroids·A PolettiL Martini
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·M F PerutzA Lesk
Apr 30, 2002·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
Aug 8, 2002·Human Molecular Genetics·Andrew P LiebermanKenneth H Fischbeck
Sep 5, 2002·Journal of Neuroscience Research·Cynthia L JordanRobert J Handa
Sep 5, 2002·Cell Motility and the Cytoskeleton·Jennifer A JohnstonRon R Kopito
Oct 22, 2002·The Journal of Biological Chemistry·Jessica L Walcott, Diane E Merry
Mar 26, 2003·Human Molecular Genetics·J Paul TaylorKenneth H Fischbeck
May 6, 2003·Science·Majid HafezparastElizabeth M C Fisher
May 21, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erica S Chevalier-LarsenDiane E Merry
Jul 24, 2004·Nature Medicine·Christopher A Ross, Michelle A Poirier
Oct 8, 2004·The EMBO Journal·Carina I HolmbergRichard I Morimoto
Dec 21, 2004·Journal of Neurochemistry·T U MarronA Poletti
Jan 22, 2005·Brain : a Journal of Neurology·Hiroaki AdachiGen Sobue
Jun 28, 2005·Nature Genetics·Brinda RavikumarDavid C Rubinsztein

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Citations

Nov 8, 2012·Cellular and Molecular Life Sciences : CMLS·Dong WangP Robin Hiesinger
Feb 20, 2013·Journal of Molecular Neuroscience : MN·Anna Rocchi, Maria Pennuto
May 11, 2012·Journal of Pediatric Endocrinology & Metabolism : JPEM·Alexis Parada-BustamanteAndrea Castro
Nov 18, 2015·Journal of Molecular Neuroscience : MN·Paola RusminiAngelo Poletti
Nov 19, 2015·Journal of Molecular Neuroscience : MN·Carlo RinaldiLinda Greensmith
Jan 22, 2011·Biology of the Cell·Daniela SauAngelo Poletti
Jun 22, 2012·Neural Plasticity·Fumiaki TanakaGen Sobue
Nov 9, 2011·Progress in Neurobiology·Fabio Sambataro, Maria Pennuto
Mar 17, 2015·Molecular and Cellular Neurosciences·Constanza J Cortes, Albert R La Spada
Jan 20, 2017·Molecular Neurobiology·Eva Mª Pérez-VillegasJosé A Armengol
Aug 15, 2020·Frontiers in Aging Neuroscience·Riccardo CristofaniAngelo Poletti
Dec 18, 2020·Frontiers in Neuroanatomy·Eva M Pérez-VillegasJosé A Armengol
Jun 18, 2021·Frontiers in Oncology·Margherita PiccolellaElio Messi

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