Autophagy receptor defects and ALS-FTLD

Majcher, Veronika; Goode, Alice; James, Victoria; Layfield, Robert

doi:10.1016/j.mcn.2015.01.002

Cited by 86 publications

(73 citation statements)

References 97 publications

(6 reference statements)

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“…Mutations in genes that encode PINK1 and Parkin, machinery that remove damaged mitochondria from the cell, lead to a juvenile onset form of Parkinson’s Disease (Kitada et al, 1998; Valente et al, 2004). Mutations in genes that encode autophagy receptors optineurin, p62, and ubiquilin-2 cause ALS (Deng et al, 2011; Fecto et al, 2011; Majcher et al, 2015; Maruyama et al, 2010). Optineurin and p62 recruit ubiquitinated cargoes to autophagosomes via their LC3-interacting regions (LIR), whereas ubiquilin-2 lacks a characterized LIR and likely interacts with LC3 indirectly (Majcher et al, 2015; Rothenberg et al, 2010).…”

Section: Autophagy In Axon Degenerationmentioning

confidence: 99%

Mechanisms of neuronal homeostasis: Autophagy in the axon

Maday

2016

Brain Research

103

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Autophagy is an evolutionarily conserved lysosomal degradation pathway that removes damaged organelles and protein aggregates from the cytoplasm. Being post-mitotic, neurons are particularly vulnerable to the accumulation of proteotoxins and are thus heavily dependent on autophagy to maintain homeostasis. In fact, CNS-specific and neuron-specific loss of autophagy is sufficient to cause neurodegeneration in mice. Further, mutations in PINK1 and Parkin, proteins that selectively remove damaged mitochondria, cause Parkinson's disease, linking defective autophagy with neurodegenerative disease in humans. This review provides an overview of the mechanisms of autophagy in the axon and the role of neuronal autophagy in axonal homeostasis and degeneration. The pathway for autophagosome biogenesis and maturation along the axon will be discussed as well as several key insights revealing the diverse functions of axonal autophagy. Evidence linking altered autophagy with axonal degeneration and neuronal death will be presented. Appropriate manipulation of autophagy may lead to promising therapeutics for neurodegenerative diseases.

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Section: Autophagy In Axon Degenerationmentioning

confidence: 99%

Mechanisms of neuronal homeostasis: Autophagy in the axon

Maday

2016

Brain Research

103

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“…An important aspect contributing to altered TDP-43 proteostasis is impairment of the ubiquitin proteasome system, autophagy and stress granule pathways in ALS (Janssens and Van Broeckhoven, 2013;Majcher et al, 2015). Protein deposition is characteristic of several neurological diseases, where a failure to clear excess and aggregating cellular proteins is associated with neuronal dysfunction and clinical symptom severity (Grad et al, 2015;Pievani et al, 2014).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Usurping key RNA binding proteins or degrading stress granules can facilitate viral replication. Formation of stress granules has also increasingly been implicated in ALS pathology (Majcher et al, 2015).…”

Section: Alterations In the Proteasome System Promotes Ervk Viral Promentioning

confidence: 99%

TDP-43 regulates endogenous retrovirus-K viral protein accumulation

Manghera

Ferguson-Parry

Douville

2016

Neurobiology of Disease

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“…Pathogene Mutationen in GRN und TREM2 legen eine kausale Rolle der Mikroglia bei FTLD nahe, weil beide Proteine besonders in Mikroglia exprimiert werden und deren Aktivierung und Phagozytosefähigkeit beeinflussen [27,33,34].…”

Section: Neuroinflammationunclassified

“…Kürzlich wurden heterozygote Varianten in TREM2 als Risikofaktor für AD und FTLD entdeckt [27]. Sehr seltene homozygote TREM2-Mutationen lösen atypische FTLD mit Knochenzysten aus (erstmals beschrieben als Nasu-HakolaKrankheit).…”

Section: Neuroinflammationunclassified