The Ca2+-activated chloride channel ANO1/TMEM16A: An emerging therapeutic target for epithelium-originated diseases?

Autor: Kewei Wang, Zongtao Liu, Yani Liu
Rok vydání: 2021
Předmět:
PASMC
pulmonary artery smooth muscle cells

PIP2
phosphatidylinositol 4
5-bisphosphate

ASM
airway smooth muscle

Drug target
ANO1
Review
HNSCC
head and neck squamous cell carcinoma

HTS
high-throughput screening

CaCCs
Ca2+ activated chloride channels

0302 clinical medicine
ENaC
epithelial sodium channels

IPAH
idiopathic pulmonary arterial hypertension

General Pharmacology
Toxicology and Pharmaceutics

BBB
blood–brain barrier

VGCC
voltage gated calcium channel

VRAC
volume regulated anion channel

Cancer
0303 health sciences
biology
Smooth muscle contraction
ICC
interstitial cells of Cajal

GI
gastrointestinal

Phenotype
DRG
dorsal root ganglion

VSMC
vascular smooth muscle cells

medicine.anatomical_structure
030220 oncology & carcinogenesis
Chloride channel
ANO1
anoctamin-1

ESCC
esophageal squamous cell carcinoma

NF-κB
nuclear factor κB

PAH
pulmonary arterial hypertension

Signal transduction
CAMK
Ca2+/calmodulin-dependent protein kinase

Anoctamin-1
CaCCinh-A01
FRT
fisher rat thyroid

PKD
polycystic kidney disease

RM1-950
Cystic fibrosis
ER
endoplasmic reticulum

GIST
gastrointestinal stromal tumor

03 medical and health sciences
Channelopathy
TGF-β
transforming growth factor-β

medicine
CFTR
cystic fibrosis transmembrane conductance regulator

T16Ainh-A01
030304 developmental biology
CF
cystic fibrosis

TMEM16A
Ang II
angiotensin II

business.industry
PAR2
protease activated receptor 2

medicine.disease
YFP
yellow fluorescent protein

Epithelium
EGFR
epidermal growth factor receptor

Ca2+-activated Cl– channels (CaCCs)
GPCR
G-protein coupled receptor

biology.protein
Therapeutics. Pharmacology
business
Neuroscience
MAPK
mitogen-activated protein kinase
Zdroj: Acta Pharmaceutica Sinica B, Vol 11, Iss 6, Pp 1412-1433 (2021)
Acta Pharmaceutica Sinica. B
ISSN: 2211-3835
DOI: 10.1016/j.apsb.2020.12.003
Popis: Anoctamin 1 (ANO1) or TMEM16A gene encodes a member of Ca2+ activated Cl– channels (CaCCs) that are critical for physiological functions, such as epithelial secretion, smooth muscle contraction and sensory signal transduction. The attraction and interest in ANO1/TMEM16A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases, including asthma, neuropathic pain, hypertension and cancer. However, the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target. This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools, hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation.
Graphical abstract The abnormal expression or dysfunction of Ca2+ activated Cl– channel anoctamin 1 (ANO1) is involved in pathological phenotypes and diseases, suggesting that pharmacological modulation of ANO1 may serve as therapeutic potential and strategy.Image 1
Databáze: OpenAIRE