Food restriction-induced autophagy modulates degradation of mutant SOD1 in an amyotrophic lateral sclerosis mouse model

Zhang, Kunxi; Shi, Pengxiao; An, Ting; Wang, Qian; Wang, Jingjing; Li, Zhongyao; Duan, Weisong; Li, Chunyan; Guo, Yansu

doi:10.1016/j.brainres.2013.04.050

Cited by 23 publications

(11 citation statements)

References 29 publications

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“…Autophagy is also impaired by ALS-associated mutations in TBK1, a kinase responsible for phosphorylation of SQSTM1 at serine 403 (Oakes et al, 2017). However, the role of autophagy in ALS remains elusive (Nguyen et al, 2018), as some reports suggest thatin ALS cases caused by mutations of superoxide dismutase 1 (SOD1)autophagy is neuroprotective at early stages of the disease but deleterious in the advanced stages (Rudnick et al, 2017;Zhang et al, 2013). This parallels the dual role of aggregated mutant SOD1 (mSOD1) in autophagy, as it upregulates autophagy initiation, while impairing axonal transport of the autophagosome and its fusion with the lysosome.…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

p62/SQSTM1 – steering the cell through health and disease

Sánchez‐Martín

Komatsu

2018

Journal of Cell Science

227

179

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SQSTM1 (also known as p62) is a multifunctional stress-inducible scaffold protein involved in diverse cellular processes. Its functions are tightly regulated through an extensive pattern of post-translational modifications, and include the isolation of cargos degraded by autophagy, induction of the antioxidant response by the Keap1-Nrf2 system, as well as the regulation of endosomal trafficking, apoptosis and inflammation. Accordingly, malfunction of SQSTM1 is associated with a wide range of diseases, including bone and muscle disorders, neurodegenerative and metabolic diseases, and multiple forms of cancer. In this Review, we summarize current knowledge regarding regulation, post-translational modifications and functions of SQSTM1, as well as how they are dysregulated in various pathogenic contexts.

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Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

p62/SQSTM1 – steering the cell through health and disease

Sánchez‐Martín

Komatsu

2018

Journal of Cell Science

227

179

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“…Several studies have shown that p62 accumulates progressively in the spinal cord (Mizuno et al, 2006; Gal et al, 2007; Zhang et al, 2013) and brainstem (An et al, 2014) of SOD1 mice. Immunostaining demonstrated that p62 and SOD1 co-localizes in aggregates in affected cells of familial mutant SOD1 mice, however p62 does not interact with wildtype SOD1 (Gal et al, 2007).…”

Section: Proteins Associated With Only Als or Ftdmentioning

confidence: 99%

Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum

Shahheydari

Ragagnin

Walker

et al. 2017

Front. Mol. Neurosci.

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Protein homeostasis, or proteostasis, has an important regulatory role in cellular function. Protein quality control mechanisms, including protein folding and protein degradation processes, have a crucial function in post-mitotic neurons. Cellular protein quality control relies on multiple strategies, including molecular chaperones, autophagy, the ubiquitin proteasome system, endoplasmic reticulum (ER)-associated degradation (ERAD) and the formation of stress granules (SGs), to regulate proteostasis. Neurodegenerative diseases are characterized by the presence of misfolded protein aggregates, implying that protein quality control mechanisms are dysfunctional in these conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that are now recognized to overlap clinically and pathologically, forming a continuous disease spectrum. In this review article, we detail the evidence for dysregulation of protein quality control mechanisms across the whole ALS-FTD continuum, by discussing the major proteins implicated in ALS and/or FTD. We also discuss possible ways in which protein quality mechanisms could be targeted therapeutically in these disorders and highlight promising protein quality control-based therapeutics for clinical trials.

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“…Down regulation of X-box-binding protein-1 (XBP-1) stimulated autophagy in mutant SOD1 mice, resulting in motor neuron protection and disease improvement (Hetz et al, 2009). Initial reports showed contradictory results upon treatment with general autophagy enhancers, such as lithium (Fornai et al, 2008; Pizzasegola et al, 2009) and rapamycin (Zhang et al, 2011), but several recent studies have demonstrated beneficial effects of enhancing autophagy in mutant SOD1 mice and other mouse models (Castillo et al, 2013; Kim et al, 2013a; Wang et al, 2012; Wang et al, 2013a; Zhang et al, 2013; Zhang et al, 2014). The therapies tested so far in ALS have been aimed at potentiating general macroautophagy mechanisms and not mitophagy specifically.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Exploring new pathways of neurodegeneration in ALS: The role of mitochondria quality control

Palomo

Manfredi

2015

Brain Research

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Neuronal cells are highly dependent on mitochondria, and mitochondrial dysfunction is associated with neurodegenerative diseases. As perturbed mitochondrial function renders neurons extremely sensitive to a wide variety of insults, such as oxidative stress and bioenergetic defects, mitochondrial defects can profoundly affect neuronal fate. Several studies have linked ALS with mitochondrial dysfunction, stemming from observations of mitochondrial abnormalities, both in patients and in cellular and mouse models of familial forms of ALS. Mitochondrial changes have been thoroughly investigated in mutants of superoxide dismutase 1 (SOD1), one of the most common causes of familial ALS, for which excellent cellular and animal models are available, but recently evidence is emerging also in other forms of ALS, both familial and sporadic. Mitochondrial defects in ALS involve many critical physiopathological processes, from defective bioenergetics to abnormal calcium homeostasis, to altered morphology and impaired trafficking. In this review, we summarize established evidence of mitochondrial dysfunction in ALS, especially in SOD1 mutant models of familial ALS. The main focus of the review is on defective mitochondrial quality control (MQC) in ALS. MQC operates at multiple levels to clear damaged proteins through proteostasis and to eliminate irreparably damaged organelles through mitophagy. However, since ALS motor neurons progressively accumulate damaged mitochondria, it is plausible that the MQC is ineffective or overwhelmed by excessive workload imposed by the chronic and extensive mitochondrial damage.

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Food restriction-induced autophagy modulates degradation of mutant SOD1 in an amyotrophic lateral sclerosis mouse model

Cited by 23 publications

References 29 publications

p62/SQSTM1 – steering the cell through health and disease

p62/SQSTM1 – steering the cell through health and disease

Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum

Exploring new pathways of neurodegeneration in ALS: The role of mitochondria quality control

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