Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord

Anagnostou, Georgia; Akbar, Mohammed T.; Paul, Praveen; Angelinetta, Claire; Steiner, Timothy J.; Belleroche, Jacqueline de

doi:10.1016/j.neurobiolaging.2008.07.005

Cited by 122 publications

(114 citation statements)

References 106 publications

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“…Furthermore, the motor neurons that survive in the spinal cord at disease end stage have particularly enhanced levels of HSPB8 protein in 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64association with soluble mutant SOD1 (Crippa, et al, 2010b). Similar data have been reported in autopsy specimens of ALS patients spinal cord (Anagnostou, et al, 2010). It must be noted that in mouse spinal cord, HSPB8 expression level decline with age (Crippa, et al, 2010b), suggesting that motor neuronal cells may become more vulnerable to misfolded protein toxicity during aging, as a result of low levels of this pro-autophagic protein.…”

Section: C) Autophagysupporting

confidence: 69%

The Role of the Protein Quality Control System in SBMA

et al. 2015

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Spinal and Bulbar Muscular Atrophy (SBMA) or Kennedy's disease is an X-linked disease associated with the expansion of the CAG triplet repeat present in exon-1 on the androgen receptor (AR) gene. This results in the production of a mutant AR containing an elongated polyglutamine tract (polyQ) in its N-terminus. Interestingly, the ARpolyQ becomes toxic only after its activation by the natural androgenic ligands, possibly because of aberrant androgen-induced conformational changes of the ARpolyQ, which generate misfolded species. These misfolded ARpolyQ species must be cleared from motoneurons and muscle cells, and this process is mediated by the protein quality control (PQC) system. Experimental evidence suggested that failure of the PQC pathways occurs in disease, leading to ARpolyQ accumulation and toxicity in the target cells. In these review we summarized the overall impact of mutant and misfolded ARpolyQ on the PQC system and described how molecular chaperons and the degradative pathways (ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), and the unfolded protein response (UPR), which activates the endoplasmic reticulum-associated degradation (ERAD)) are differentially affected in SBMA. We also extensively and critically reviewed several molecular and pharmacological approaches proposed to restore a global intracellular activity of the PQC system. Collectively, these data suggest that the fine and delicate equilibrium existing among the different players of the PQC system could be restored in a therapeutic perspective by the synergic/additive activities of compounds designed to tackle sequential or alternative steps of the intracellular defense mechanisms triggered against proteotoxic misfolded species.

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Section: C) Autophagysupporting

confidence: 69%

The Role of the Protein Quality Control System in SBMA

et al. 2015

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“…The reported upregulation of HspB1 and HspB8 chaperone expression in the lumbar spinal cord of 39 ALS cases (4 of which were familial ALS cases) compared to 19 control samples may be an indication of such a protective response (Anagnostou et al, 2010). …”

Section: Loss Of Protein Homeostasis In Alsmentioning

confidence: 99%

Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?

Webster

Smith

Shaw

et al. 2017

Front. Mol. Neurosci.

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Protein homeostasis (proteostasis), the correct balance between production and degradation of proteins, is essential for the health and survival of cells. Proteostasis requires an intricate network of protein quality control pathways (the proteostasis network) that work to prevent protein aggregation and maintain proteome health throughout the lifespan of the cell. Collapse of proteostasis has been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disorder. Here, we review the evidence linking dysfunctional proteostasis to the etiology of ALS and discuss how ALS-associated insults affect the proteostasis network. Finally, we discuss the potential therapeutic benefit of proteostasis network modulation in ALS.

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“…Furthermore, Bc inhibits the aggregation of glial acidic fibrillary protein (GAFP) and -syn which are associated with Alexander and Parkinson's disease (PD) pathologies, respectively [167,168]. Hsp20 and Hsp22 are also present at increased levels following neuronal stress associated with AD, PD, and ALS [169][170][171][172][173]. Hsp27 is also upregulated in AD and Neuman-Pick diseases [70].…”

Section: The Role Of Shsps In Neurodegenerative Diseasementioning

confidence: 99%

Small heat-shock proteins: important players in regulating cellular proteostasis

Treweek

Meehan

Ecroyd

et al. 2014

Cell. Mol. Life Sci.

180

177

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Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of posttranslational modifications in sHsp chaperone function, particularly in the context of disease. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Abstract (word count = 159)Small heat-shock proteins (sHsps) are a diverse family of intracellular molecular chaperone proteins that play a critical role in preventing protein unfolding, misfolding and aggregation, particularly under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) and thereby avoid the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. There has been much research into the structure and mechanism of chaperone action of sHsps over approximately the past 30 years, and significant progress has been made of late, however, there are still many unanswered questions relating to these aspects of sHsps. In this review, we outline some of the recent advances in understanding the structure and function of mammalian sHsps, particularly in the context of their many and varied roles in disease.

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Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord

Cited by 122 publications

References 106 publications

The Role of the Protein Quality Control System in SBMA

The Role of the Protein Quality Control System in SBMA

Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?

Small heat-shock proteins: important players in regulating cellular proteostasis

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