<i>HSJ1</i>
            -related hereditary neuropathies

Gess, Burkhard; Auer‐Grumbach, Michaela; Schirmacher, Anja; Strom, Tim M.; Zitzelsberger, Manuela; Rudnik‐Schöneborn, Sabine; Röhr, Dominik; Halfter, Hartmut; Young, Peter; Senderek, Jan

doi:10.1212/wnl.0000000000000966

Cited by 42 publications

(44 citation statements)

References 36 publications

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“…In 2012, Blumen et al reported mutations in HSJ1 in a consanguineous Moroccan family with dHMN [48]. Recently, a second mutation was identified in a Turkish family also with dHMN [49]. Both mutations are homozygous and are located at donor splice sites, leading to the loss of HSJ1 protein expression.…”

Section: Hsj1 (Dnajb2)mentioning

confidence: 99%

“…Both mutations are homozygous and are located at donor splice sites, leading to the loss of HSJ1 protein expression. A third mutation in HSJ1 has also been identified recently, this time in a family with Charcot-Marie-Tooth type 2 (CMT2) [49]. CMT2 closely resembles dHMN but patients have sensory abnormalities in addition to motor involvement.…”

Section: Hsj1 (Dnajb2)mentioning

confidence: 99%

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Molecular chaperones and neuronal proteostasis

Smith¹,

Li²,

Cheetham³

2015

Seminars in Cell & Developmental Biology

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Protein homeostasis (proteostasis) is essential for maintaining the functionality of the proteome. The disruption of proteostasis, due to genetic mutations or an age-related decline, leads to aberrantly folded proteins that typically lose their function. The accumulation of misfolded and aggregated protein is also cytotoxic and has been implicated in the pathogenesis of neurodegenerative diseases. Neurons have developed an intrinsic protein quality control network, of which molecular chaperones are an essential component. Molecular chaperones function to promote efficient folding and target misfolded proteins for refolding or degradation. Increasing molecular chaperone expression can suppress protein aggregation and toxicity in numerous models of neurodegenerative disease; therefore, molecular chaperones are considered exciting therapeutic targets. Furthermore, mutations in several chaperones cause inherited neurodegenerative diseases. In this review, we focus on the importance of molecular chaperones in neurodegenerative diseases, and discuss the advances in understanding their protective mechanisms.

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Section: Hsj1 (Dnajb2)mentioning

confidence: 99%

Section: Hsj1 (Dnajb2)mentioning

confidence: 99%

Molecular chaperones and neuronal proteostasis

Smith¹,

Li²,

Cheetham³

2015

Seminars in Cell & Developmental Biology

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“…In this case, the expression of DNAJB2 was dampened in fibroblasts from the patients and overexpression of the protein reduced the formation of inclusions in a neuronal cellular model, suggesting DNAJB2 is active in motor neurons and/or muscle (Blumen et al, 2012). Two additional homozygous mutations were later described in the DNAJB2 gene, c.229+1G>A and c.14A>G (p.Y5C), in a family diagnosed with dHMN (dHMN5) and another with CMT2 (CMT2T), respectively (Gess et al, 2014). More recently, a homozygous large deletion was reported in a family with spinal muscular atrophy and parkinsonism, broadening the clinical spectrum of DNAJB2 related neuropathies (Sanchez et al, 2016).…”

Section: The Growing List Of Chaperones Involved In Distal Hereditarymentioning

confidence: 99%

Chaperonopathies: Spotlight on Hereditary Motor Neuropathies

Lupo

Aguado

Knecht

et al. 2016

Front. Mol. Biosci.

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Distal hereditary motor neuropathies (dHMN) are a group of rare hereditary neuromuscular disorders characterized by an atrophy that affects peroneal muscles in the absence of sensory symptoms. To date, 23 genes are thought to be responsible for dHMN, four of which encode chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family; and HSPB1, HSPB3, and HSPB8, encoding three members of the small heat shock protein family. While around 30 different mutations in HSPB1 have been identified, the remaining three genes are altered in many fewer cases. Indeed, a mutation of HSPB3 has only been described in one case, whereas a few cases have been reported carrying mutations in DNAJB2 and HSPB8, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the K141 residue in the HSPB8 chaperone. Hence, their rare occurrence makes it difficult to understand the pathological mechanisms driven by such mutations in this neuropathy. Chaperones can assemble into multi-chaperone complexes that form an integrated chaperone network within the cell. Such complexes fulfill relevant roles in a variety of processes, such as the correct folding of newly synthesized proteins, in which chaperones escort them to precise cellular locations, and as a response to protein misfolding, which includes the degradation of proteins that fail to refold properly. Despite this range of functions, mutations in some of these chaperones lead to diseases with a similar clinical profile, suggesting common pathways. This review provides an overview of the genetics of those dHMNs that share a common disease mechanism and that are caused by mutations in four genes encoding chaperones: DNAJB2, HSPB1, HSPB3, and HSPB8.

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“…1 Since then, two other families with different HSJ1 mutations have been described: one with a dHMN phenotype and the other with a Charcot-Marie-Tooth disease type 2 (CMT2) phenotype. 2 We identified the HSJ1 c.352+1G>A mutation in 10 patients who underwent long-lasting follow-up. We describe their phenotype and clinical evolution.…”

Section: Introductionmentioning

confidence: 97%