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

Related Links:

The eye-of-the-tiger sign has been classically associated with pantothenate kinase-associated neurodegeneration (PKAN), also called neurodegeneration with brain iron accumulation (NBIA) type 1, and formerly known as Hallervorden-Spatz syndrome [1]. Two clinical forms of PKAN exist: the classic phenotype presents within the first decade of life and rapidly progresses, while the atypical phenotype manifests in the second to third decade of life and slowly deteriorates. Clinical features of PKAN include chorea, dystonia, bradykinesia, tremor, gait dysfunction, ataxia, rigidity, and dementia [1,2].
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
Recently mutations in IRF2BPL gene with a complex neurological phenotype including combination of progressive neurodevelopmental delay, seizures, cerebellar ataxia, dystonia and pyramidal signs were reported in 2 independent studies [1,2].
Source: Parkinsonism and Related Disorders - Category: Neurology Authors: Tags: Correspondence Source Type: research
ConclusionOur LC-MS/MS assay may be necessary to accurately quantify residual GALT activities below 5%. The data suggest that patients with>1% residual activity are less likely to develop diet-independent long-term complications. However, much larger sample sizes are needed to properly correlate the clinical phenotype in patients with residual enzyme activities between 0.1 and 5%.
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research
This article provides the reader with an overview of the most important groups of genetic movement disorders. Genetic Parkinson syndromes, dystonia, essential tremor, genetic chorea, cerebellar ataxia and hereditary spastic paraplegia are dealt with in detail. For a better understanding individual genetic terms are explained and differences in molecular genetic diagnostics are presented. PMID: 30645659 [PubMed - as supplied by publisher]
Source: Der Nervenarzt - Category: Neurology Authors: Tags: Nervenarzt Source Type: research
AbstractNiemann-Pick disease type C (NPC) is a lysosomal storage disorder that presents with a spectrum of clinical manifestations from infancy and childhood or in early or mid-adulthood. Progressive neurological symptoms including ataxia, dystonia and vertical gaze palsy are a hallmark of the disease, and psychiatric symptoms such as psychosis and mood disorders are common. These latter symptoms often present early in the course of NPC and thus these patients are often diagnosed with a major psychotic or affective disorder before neurological and cognitive signs present and the diagnosis is revised. The commonalities and ...
Source: CNS Drugs - Category: Neurology Source Type: research
We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17 and present detailed neuropsychological assessment for the first time. A 44-year-old doctor presented with 18-month history of behavioral problems. She slowed down, became apathetic, and unable to multitask. She became more irritable and short tempered, and her work performance deteriorated. Brain MRI showed cerebellar atrophy and cerebellar hypometabolism was noted on FDG-PET. A sister developed personality changes at age 45 with apathy, and had problems with memory and social skills; another sister ...
Source: Cerebellum - Category: Neuroscience Authors: Tags: Cerebellum Source Type: research
We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17 and present detailed neuropsychological assessment for the first time. A 44-year-old doctor presented with 18-month history of behavioral problems. She slowed down, became apathetic, and unable to multitask. She became more irritable and short tempered, and her work performance deteriorated. Brain MRI showed cerebellar atrophy and cerebellar hypometabolism was noted on FDG-PET. A sister developed personality changes at age 45 with apathy, and had problems with memory and social skills; another sister ...
Source: The Cerebellum - Category: Neurology Source Type: research
AbstractPrimary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by symmetrical and bilateral brain calcification. It is typically inherited as an autosomal dominant disorder, and de novo variants have also been described. Interestingly, just recent studies have reported the first autosomal recessive PFBC-causative gene. PFBC patients exhibit high clinical heterogeneity including Parkinsonism, dystonia, ataxia, depression, and migraine. Mice studies, an important research tool, have been a breakthrough in increasing the understanding of PFBC ’s main signs and symptoms, and many f...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common spinocerebellar ataxia (SCA) worldwide. SCA3 presents with cerebellar ataxia in association with pyramidal signs, peripheral amyotrophy, nystagmus, ophthalmoparesis, fasciculations of the face and tongue, dystonia and parkinsonism. Oromandibular dystonia (OMD) with facial grimacing (FG) in SCA3 has seldom been reported in the literature and in series of SCA3 patients.
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Clinical short communication Source Type: research
Homozygous sequestomosome-1 gene mutations have been recently linked to neurodegeneration with dystonia, ataxia and gaze palsy. Seven affected families were identified thus far.
Source: Parkinsonism and Related Disorders - Category: Neurology Authors: Tags: Short communication Source Type: research
More News: Ataxia | Brain | Calcium | Cerebellum | Chloride | Dystonia | Gastroschisis Repair | Neurology