Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2 mutations cause CMT type 2A by altering mitochondrial fusion and trafficking along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT type which in most cases is characterized by early onset and rather severe course. GDAP1 mutations also alter fission, fusion and transport of mitochondria and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR-CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its heterozygous mutations lead to early-onset and progressive dominant optic atrophy which may be complicated by other neurological symptoms including peripheral neuropathy. Mutations in several proteins fundamental for the axonal transport or forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT, distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed, mitochondrial transport involves directly or indirectly components of the kinesin superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2), implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such as heat shock proteins (HSPs) also have a fundamental role in mitochondrial transport and mutations in some of related encoding genes cause peripheral neuropathy (TUBB3, NEFL, HSPB1, HSPB8, HSPB3, DNAJB2). In this review, we address the abnormalities in mitochondrial dynamics and their role in determining CMT disease and related neuropathies.
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PMID:Mitochondrial dynamics and inherited peripheral nerve diseases. 2584 51

In recent years, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has emerged as a substitute for PFOS with large demand and application in the Chinese market. However, little is known about potential developmental effects of OBS. In this study, zebrafish embryos were acutely exposed to different concentrations of OBS and the positive control PFOS for a comparative developmental toxicity assessment. OBS caused hatching delays, body axis curvature, neurobehavioral inhibition and abnormal cardiovascular development. These organismal effects were accompanied by change of development related genes expression profile, in which some cases were similar to PFOS. Overall, the toxic effects induced by OBS were generally milder than that of PFOS. Further investigation suggested that both OBS and PFOS disrupted ciliogenesis, evidenced by the ciliary immunostaining, changes in gene expression of kinesin family, dynein arm family and tubulin family members, as well as downregulation of the abundance of motor proteins including KIF3C, DYNC1H1 and DYNC1LI1. The influence of PFOS was stronger than that of OBS on ciliary genes and proteins. Molecular docking analysis revealed that both OBS and PFOS fitted into the motor proteins tightly, but binding affinity between OBS and motor proteins was lower than PFOS. Collectively, OBS and PFOS may act on ciliary motor proteins to interfere with ciliogenesis, leading to ciliary dysfunction and providing a novel probable action mode linked to developmental toxicity. This raises concerns regarding the health risks of the novel PFOS alternative OBS.
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PMID:Developmental toxicity of the novel PFOS alternative OBS in developing zebrafish: An emphasis on cilia disruption. 3322 14