Anoctamins (TMEM16 proteins): Functions and involvement in neurologic disease

Anoctamins (anion channels with 8 transmembrane domains [ANO]), also known as transmembrane proteins with 16 domains (TMEM16), are highly conserved intracellular calcium (Ca2+)–activated proteins with multiple cellular functions. The ANO/TMEM16 family includes 10 members (ANO1/TMEM16A to ANO10/TMEM16K), with distinct distributions in tissues. Some of these proteins, such as ANO1 and ANO2, are prototypical Ca2+-activated chloride (Cl–) channels. Others, including ANO6, mediate Ca2+-dependent exposure of phospholipids that are normally expressed in the inner leaflet of the membrane to the extracellular surface; this process is called phospholipid scrambling or scramblase activity. Anoctamins are involved in regulation of neuronal cell excitability, epithelial secretion, smooth muscle contraction, repair of skeletal muscle membrane, and tumorigenesis. The structure, mechanism of activation, and functions of anoctamins have been reviewed recently.1–6 Anoctamins contribute to heat-induced pain7,8 and modulate excitability in neurons in the dorsal root ganglia (DRG),9 hippocampus,10 and cerebellum.11 Mutations affecting different anoctamins have been linked to several neurologic disorders, including muscle disease,12–15 cerebellar ataxia,16–18 and dystonia.19,20 Thus, anoctamins constitute a potential therapeutic target in a wide range of neurologic disorders.
Source: Neurology - Category: Neurology Authors: Tags: CLINICAL IMPLICATIONS OF NEUROSCIENCE RESEARCH Source Type: research

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Abstract Huntington's disease (HD) is an autosomal neurodegenerative disease characterized by chorea, dystonia, motor ataxia, cognitive decline and psychiatric disorders with gradual loss of nerve cells and has no existing cure for the disease. In the present study, a mitochondrial toxin, 3-nitropropionic acid (3-NP) is used to induce HD like symptoms in rats. Tetramethylpyrazine is one of the active ingredients of Chuan Xiong which was reported to have neurotrophic and neuroprotective activities. The present study was designed to evaluate the role of TMP on 3-NP induced behavioral, biochemical, neurochemical, and...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
Publication date: September 2018Source: Molecular Genetics and Metabolism Reports, Volume 16Author(s): Kishore R. Kumar, Gautam Wali, Ryan L. Davis, Amali C. Mallawaarachchi, Elizabeth E. Palmer, Velimir Gayevskiy, Andre E. Minoche, David Veivers, Marcel E. Dinger, Alan Mackay-Sim, Mark J. Cowley, Carolyn M. SueAbstractZellweger syndrome spectrum disorders are caused by mutations in any of at least 12 different PEX genes. This includes PEX16, an important regulator of peroxisome biogenesis. Using whole genome sequencing, we detected previously unreported, biallelic variants in PEX16 [NM_004813.2:c.658G>A, p.(Ala220Thr) ...
Source: Molecular Genetics and Metabolism Reports - Category: Genetics & Stem Cells Source Type: research
Conclusion: Dystonia in SCA3 is frequent and displays highly variable clinical profiles and severity grades. Dystonia is therefore a present symptom in SCA3, which may precede the SCA3 classic symptoms. Dystonia diagnosis is yet to be properly recognized within SCA3 patient. PMID: 30008965 [PubMed]
Source: The Open Neurology Journal - Category: Neurology Tags: Open Neurol J Source Type: research
Abstract Movement disorders are reported in idiopathic autism but the extent to which comparable movement disorders are found in syndromic/co-morbid autism is unknown. A systematic search of Medline, Embase, PsychINFO and CINAHL on the prevalence of specific movement disorder in syndromic autism associated with specific genetic syndromes identified 16 papers, all relating to Angelman syndrome or Rett syndrome. Prevalence rates of 72.7-100% and 25.0-27.3% were reported for ataxia and tremor, respectively, in Angelman syndrome. In Rett syndrome, prevalence rates of 43.6-50% were reported for ataxia and 27.3-48.3% fo...
Source: Journal of Autism and Developmental Disorders - Category: Psychiatry Authors: Tags: J Autism Dev Disord Source Type: research
Neuropediatrics DOI: 10.1055/s-0038-1667024 ATP1A3 mutations have now been recognized in infants, children, and adults presenting with a diverse group of neurological phenotypes, including rapid-onset dystonia-parkinsonism, alternating hemiplegia of childhood, and most recently, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. The phenotypic spectrum of ATP1A3-related neurological disorders continues to expand. In this case study, we report on early life epilepsy with episodic apnea potentially secondary to ATP1A3 mutation in a Tunisian child. [...] Georg Thieme Verlag KG ...
Source: Neuropediatrics - Category: Neurology Authors: Tags: Short Communication Source Type: research
We report here a family which places a caveat on genetic counselling for mtDNA disorders. The proband is a 63 year old woman with m.14459G>A associated dystonia/spasticity/ataxia. The m.14459G>A mutation was detected at homoplasmic/near homoplasmic levels in her muscle tissue and fibroblasts, but does not appear to have been passed on to any of her offspring. To our knowledge this is the first report of complete selection against a homoplasmic variant within maternally transmitted mtDNA. It is not clear if this novel phenomenon occurred by random chance or by another method of mitochondrial selection.
Source: Mitochondrion - Category: Biochemistry Source Type: research
Publication date: September 2018Source: Biomedicine &Pharmacotherapy, Volume 105Author(s): Ravi Chandra Sekhara Reddy Danduga, Subba Reddy Dondapati, Phani Kumar Kola, Lilly Grace, Rahil Vandana Bisky Tadigiri, Vijaya Kishore KanakarajuAbstractHuntington’s disease (HD) is an autosomal neurodegenerative disease characterized by chorea, dystonia, motor ataxia, cognitive decline and psychiatric disorders with gradual loss of nerve cells and has no existing cure for the disease. In the present study, a mitochondrial toxin, 3-nitropropionic acid (3-NP) is used to induce HD like symptoms in rats. Tetramethylpyrazine is...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 7 May 2018Source: Neuroscience LettersAuthor(s): Jaclyn Beckinghausen, Roy V. SillitoeAbstractThe cerebellum has a well-established role in controlling motor functions such coordination, balance, posture, and skilled learning. There is mounting evidence that it might also play a critical role in non-motor functions such as cognition and emotion. It is therefore not surprising that cerebellar defects are associated with a wide array of diseases including ataxia, dystonia, tremor, schizophrenia, dyslexia, and autism spectrum disorder. What is intriguing is that a seemingly uniform circuit t...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
Abstract Previously, we defined DRD as a syndrome of selective nigrostriatal dopamine deficiency caused by genetic defects in the dopamine synthetic pathway without nigral cell loss. DRD-plus also has the same etiologic background with DRD, but DRD-plus patients have more severe features that are not seen in DRD because of the severity of the genetic defect. However, there have been many reports of dystonia responsive to dopaminergic drugs that do not fit into DRD or DRD-plus (genetic defects in the dopamine synthetic pathway without nigral cell loss). We reframed the concept of DRD/DRD-plus and proposed the conce...
Source: J Korean Med Sci - Category: General Medicine Authors: Tags: J Korean Med Sci Source Type: research
ATP1A3-related autosomal dominant disorders include rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss) [1]. Chorea, myoclonus and psychiatric disorders have been also described [2 –4]. AHC mainly occurs in children and consists of recurrent and fully recovering episodes of hemiplegia and dystonia in alternating sides [1]. RDP is typically monophasic and is characterized by abrupt onset and rapidly progressive asymmetric dystonia and parkinsonism, associated with predominant bulb...
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
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