Properties of FDA-approved small molecule protein kinase inhibitors

Pharmacological Research, Journal Year: 2019, Volume and Issue: 144, P. 19 - 50

Published: March 13, 2019

Language: Английский

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RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

Cell & Bioscience, Journal Year: 2020, Volume and Issue: 10(1)

Published: April 1, 2020

Abstract The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism angiogenesis. Compared with those other pathways, components PI3K/AKT/mTOR are complicated. regulatory mechanisms functions many human diseases, including ischaemic brain injury, neurodegenerative tumours. inhibitors include single-component dual inhibitors. Numerous PI3K have exhibited good results preclinical studies, some been clinically tested haematologic malignancies solid In this review, we briefly summarize research on discuss structural composition, activation, communication processes, pathogenesis diseases

Language: Английский

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Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment

CNS Neuroscience & Therapeutics, Journal Year: 2016, Volume and Issue: 23(1), P. 5 - 22

Published: Nov. 22, 2016

Summary Neurodegenerative diseases are a heterogeneous group of disorders that incurable and characterized by the progressive degeneration function structure central nervous system ( CNS ) for reasons not yet understood. Neurodegeneration is umbrella term death nerve cells loss brain tissue. Because their high energy requirements, neurons especially vulnerable to injury from dysfunctional mitochondria. Widespread damage mitochondria causes die because they can no longer produce enough energy. Several lines pathological physiological evidence reveal impaired mitochondrial dynamics play crucial roles in aging pathogenesis neurodegenerative diseases. As major intracellular organelles regulate both cell survival death, highly considered as potential target pharmacological‐based therapies. The purpose this review was present current status our knowledge understanding involvement dysfunction including Alzheimer's disease AD ), Parkinson's PD Huntington's HD amyotrophic lateral sclerosis ALS importance biogenesis novel therapeutic treatment. Likewise, we highlight concise overview key electron transport chain ETC. complexes well regulators regarding those

Language: Английский

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There's Something Wrong with my MAM; the ER–Mitochondria Axis and Neurodegenerative Diseases

Trends in Neurosciences, Journal Year: 2016, Volume and Issue: 39(3), P. 146 - 157

Published: Feb. 16, 2016

TrendsMitochondria and the ER form close physical contacts.ER–mitochondria contacts regulate functions damaged in neurodegenerative diseases.ER–mitochondria are diseases.AbstractAlzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) major diseases for which there no cures. All characterised by damage to several seemingly disparate cellular processes. The broad nature of this makes understanding pathogenic mechanisms devising new treatments difficult. Can different be linked together a common pathway function should targeted therapy? Many regulated communications that mitochondria make specialised region endoplasmic reticulum (ER; mitochondria-associated membranes or 'MAM'). Moreover, recent studies have shown disturbances ER–mitochondria occur diseases. Here, we review these findings.

Language: Английский

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α-Synuclein binds to the ER–mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production

Acta Neuropathologica, Journal Year: 2017, Volume and Issue: 134(1), P. 129 - 149

Published: March 23, 2017

α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in regulated by signalling between endoplasmic reticulum (ER) and mitochondria. This involves close physical associations two organelles that mediated binding of integral ER protein vesicle-associated membrane protein-associated B (VAPB) outer mitochondrial protein, tyrosine phosphatase-interacting 51 (PTPIP51). VAPB PTPIP51 thus act as a scaffold tether organelles. Here we show α-synuclein binds overexpression wild-type familial mutant disrupt VAPB-PTPIP51 tethers loosen ER-mitochondria associations. disruption also seen neurons derived from induced pluripotent stem cells patients harbouring pathogenic triplication gene. We loosening contacts accompanied Ca2+ exchange ATP production. Such disruptions likely be particularly damaging heavily dependent on correct signaling ATP.

Language: Английский

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The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action

Drug Discovery Today, Journal Year: 2016, Volume and Issue: 21(5), P. 802 - 818

Published: Feb. 3, 2016

Growing evidence suggests that agonists of the glucagon-like peptide 1 (GLP-1) receptor provide neuroprotection across a range experimental models Parkinson's disease (PD) and, recently, small proof-of-concept, open-label human trial exenatide in treatment moderate severity PD appeared to show persistent improvements motor and cognitive function. The underlying mechanisms action remain unclear, but as for potential use GLP-1 treating several neurodegenerative mounts, with clinical trials analogues Alzheimer's (AD) currently underway, here we review molecular neuroprotective effects laboratory their therapeutic utility particular relevance dementia (PDD).

Language: Английский

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Insulin resistance and Parkinson’s disease: A new target for disease modification?

Progress in Neurobiology, Journal Year: 2016, Volume and Issue: 145-146, P. 98 - 120

Published: Oct. 1, 2016

Language: Английский

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Targeting ERK1/2 protein-serine/threonine kinases in human cancers

Pharmacological Research, Journal Year: 2019, Volume and Issue: 142, P. 151 - 168

Published: Feb. 19, 2019

Language: Английский

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Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function

Frontiers in Endocrinology, Journal Year: 2018, Volume and Issue: 9

Published: Nov. 23, 2018

The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its 'incretin effect' in restoring glucose homeostasis diabetics, however, it now apparent that has a broader range of physiological effects the body. Both vitro and vivo studies have demonstrated GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression influence neuroprotective pathways. A substantial body evidence accumulated with respect to how analogues act restore maintain normal cellular functions. These findings prompted several clinical trials which reported improve cardiac function, lung function reduce mortality patients obstructive disease, blood pressure lipid storage, even prevent synaptic loss neurodegeneration. Mechanistically, elicits via acute elevation cAMP levels, subsequent protein kinase(s) activation, pathways well defined pancreatic β-cells insulin secretion conjunction elevated Ca2+ ATP. More recently, new shed light on additional downstream stimulated by chronic exposure, direct relevance our understanding potential therapeutic longer lasting recently developed use. In this review, we provide comprehensive description diverse roles across multiple tissues, describe discuss novel pleiotropic applications treatment human disease.

Language: Английский

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Mitochondria-associated membranes as hubs for neurodegeneration

Acta Neuropathologica, Journal Year: 2016, Volume and Issue: 131(4), P. 505 - 523

Published: Jan. 7, 2016

Language: Английский

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