The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy

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Deneubourg , C , Ramm , M , Smith , L J , Baron , O , Singh , K , Byrne , S C , Duchen , M R , Gautel , M , Eskelinen , E-L , Fanto , M & Jungbluth , H 2022 , ' The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy ' , Autophagy , vol. 18 , no. 3 , pp. 496-517 . https://doi.org/10.1080/15548627.2021.1943177

Title: The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy
Author: Deneubourg, Celine; Ramm, Mauricio; Smith, Luke J.; Baron, Olga; Singh, Kritarth; Byrne, Susan C.; Duchen, Michael R.; Gautel, Mathias; Eskelinen, Eeva-Liisa; Fanto, Manolis; Jungbluth, Heinz
Contributor organization: Molecular and Integrative Biosciences Research Programme
Biosciences
Autophagy
Biochemistry and Biotechnology
Date: 2022
Language: eng
Number of pages: 22
Belongs to series: Autophagy
ISSN: 1554-8627
DOI: https://doi.org/10.1080/15548627.2021.1943177
URI: http://hdl.handle.net/10138/345994
Abstract: Primary dysfunction of autophagy due to Mendelian defects affecting core components of the autophagy machinery or closely related proteins have recently emerged as an important cause of genetic disease. This novel group of human disorders may present throughout life and comprises severe early-onset neurodevelopmental and more common adult-onset neurodegenerative disorders. Early-onset (or congenital) disorders of autophagy often share a recognizable "clinical signature," including variable combinations of neurological, neuromuscular and multisystem manifestations. Structural CNS abnormalities, cerebellar involvement, spasticity and peripheral nerve pathology are prominent neurological features, indicating a specific vulnerability of certain neuronal populations to autophagic disturbance. A typically biphasic disease course of late-onset neurodegeneration occurring on the background of a neurodevelopmental disorder further supports a role of autophagy in both neuronal development and maintenance. Additionally, an associated myopathy has been characterized in several conditions. The differential diagnosis comprises a wide range of other multisystem disorders, including mitochondrial, glycogen and lysosomal storage disorders, as well as ciliopathies, glycosylation and vesicular trafficking defects. The clinical overlap between the congenital disorders of autophagy and these conditions reflects the multiple roles of the proteins and/or emerging molecular connections between the pathways implicated and suggests an exciting area for future research. Therapy development for congenital disorders of autophagy is still in its infancy but may result in the identification of molecules that target autophagy more specifically than currently available compounds. The close connection with adult-onset neurodegenerative disorders highlights the relevance of research into rare early-onset neurodevelopmental conditions for much more common, age-related human diseases.
Subject: 1182 Biochemistry, cell and molecular biology
autophagy
congenital disorders of autophagy
cellular trafficking
neurodegenerative disorders
neurodevelopmental disorders
CHEDIAK-HIGASHI-SYNDROME
SOD1(G93A) MOUSE MODEL
VICI SYNDROME
FRONTOTEMPORAL DEMENTIA
ALPHA-SYNUCLEIN
CENTRONUCLEAR MYOPATHY
REGULATES AUTOPHAGY
CYTOPLASMIC DYNEIN
IMPAIRS AUTOPHAGY
BRAIN-DEVELOPMENT
MICROTUBULE-ASSOCIATED PROTEIN
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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