Role of cholesterol and sphingolipids in brain development and neurological diseases

Lipids in Health and Disease, Journal Year: 2019, Volume and Issue: 18(1)

Published: Jan. 25, 2019

Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution electrical signals. For this purpose, it depends on complex network nerves are ensheathed in lipids tailored myelin; an abundant source body. The nervous system enriched with classes lipids; sphingolipids cholesterol compose major portion brain particularly form myelin. Both embedded microdomains membrane rafts functional units neuronal cell membrane. These molecules serve signaling molecules; hold roles differentiation, synaptogenesis, many others. Thus, their adequate provision active metabolism crucial importance maintenance physiological individual. In present review, we have highlighted development well association altered to neurological neurodegenerative diseases.

Language: Английский

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BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease

Medicinal Research Reviews, Journal Year: 2019, Volume and Issue: 40(1), P. 339 - 384

Published: July 26, 2019

Abstract Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder with no current cure. One of the important therapeutic approaches AD inhibition β‐site APP cleaving enzyme‐1 (BACE1), which involved in rate‐limiting step cleavage process amyloid precursor protein (APP) leading to generation neurotoxic β (Aβ) after γ‐secretase completes its function. The produced insoluble Aβ aggregates lead plaques deposition and neurodegeneration. BACE1 is, therefore, one attractive targets for treatment AD. This approach led development potent inhibitors, many were advanced late stages clinical trials. Nonetheless, high failure rate drug candidates targeting brought forefront need finding new uncover mystery behind In this review, we aim discuss most promising classes inhibitors a description analysis their pharmacodynamic pharmacokinetic parameters, more focus on that reached trials, such as MK8931, AZD‐3293, JNJ‐54861911, E2609, CNP520. addition, manuscript discusses safety concerns insignificant physiological effects, highlighted successful inhibitors. Furthermore, review demonstrates increasing evidence despite tremendous efforts results conceived latest studies suggest use treating should be reconsidered. Finally, sheds light alternative options

Language: Английский

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Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery

International Journal of Biological Sciences, Journal Year: 2019, Volume and Issue: 16(1), P. 116 - 134

Published: Dec. 6, 2019

Peripheral nerve injury is a complex condition with variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain.Peripheral nerves are fragile in nature can easily get damaged due to acute compression trauma which may lead the sensory motor functions deficits even lifelong disability.After lesion, neuronal cell body becomes disconnected from axon's distal portion site leading axonal degeneration dismantlement neuromuscular junctions targeted muscles.In spite extensive research on this aspect, complete functional recovery still remains challenge be resolved.This review highlights detailed pathophysiological events after an peripheral associated factors that either hinder promote regenerative machinery.In addition, it throws light available therapeutic strategies including supporting therapies, surgical non-surgical interventions ameliorate regeneration, survival, reinnervation targets.Despite availability various treatment options, we lacking optimal treatments for perfect regain.The need present age discover design potent compounds would able execute retrieval.In regard, plant-derived getting more attention several recent reports validate their remedial effects.A plethora plants phytochemicals have been suggested curative effects against number diseases general particular.They ray hope suffering individuals.

Language: Английский

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Applications of Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders

Materials, Journal Year: 2022, Volume and Issue: 15(3), P. 804 - 804

Published: Jan. 21, 2022

The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to existence blood-brain barrier (BBB), a closely spaced network blood vessels endothelial cells that functions prevent entry unwanted substances brain. emergence advancement nanotechnology shows favourable prospects overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties imaging agents have dimensions between 1 100 nm could potentially be used ensure enhanced efficacy, cellular uptake, specific transport, delivery molecules brain, owing their modified physico-chemical features. conjugates medicinal plants, or components known as nano phytomedicine, been gaining significance lately novel neuro-therapeutics natural abundance, promising targeted lesser potential show adverse effects. In present review, application, recent trends combined phytomedicine treatment neurological (ND) compared conventional therapies, addressed. Nanotechnology-based efforts performed bioinformatics early diagnosis well futuristic precision medicine ND also discussed context computational approach.

Language: Английский

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Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 380 - 380

Published: Jan. 4, 2025

Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides comprehensive analysis the effects PSMs on mitochondrial health, with particular emphasis therapeutic potential. Emerging evidence shows that these improve function by reducing oxidative stress, promoting biogenesis, regulating key processes such as apoptosis mitophagy. Mitochondrial dysfunction, hallmark many pathologies, neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, has shown to benefit from protective PSMs. Recent studies show can dynamics, stabilise membranes, enhance bioenergetics, offering significant promise prevention treatment mitochondrial-related diseases. The molecular mechanisms underlying effects, modulation signalling pathways direct interactions proteins, discussed. integration into strategies is highlighted promising avenue improving efficacy while minimising side commonly associated synthetic drugs. also highlights need future research elucidate specific roles individual synergistic within complex plant matrices, may further optimise utility. Overall, this work valuable insights health potential natural agents targeting dysfunction.

Language: Английский

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Nanoformulations of Herbal Extracts in Treatment of Neurodegenerative Disorders

Frontiers in Bioengineering and Biotechnology, Journal Year: 2020, Volume and Issue: 8

Published: April 7, 2020

Nanotechnology is one of the methods that have been able to influence human life in different ways and a substantial tool assists overcome multiple limitations treatment various diseases, especially neurodegenerative disorders (NDs). Various nanostructures such as polymer nanoparticles, lipid nanoliposomes, nano-micelle, carbon nanotubes (CNTs), besides vehicle systems including poly lactic-co-glycolic acid, lactoferrin, polybutylcyanoacrylate some others significantly increased effectiveness, reduced side effects, enhanced stability, improved pharmacokinetics several drugs. NDs belong group annoying debilitating involving millions people worldwide. Privious studies revealed nano formulations from number natural products curcumin (Cur), quercetin (QC), resveratrol (RSV), piperine (PIP), Ginkgo biloba, Nigella sativa showed significant effectiveness improving condition patients with NDs. The blood-brain barrier (BBB) main limitation management. In this review, we attempted discuss effects herbal-based formulation used treat diseases. summary, nanoformulations seem be NDs, alone or combination other

Language: Английский

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Plant Extracts and Phytochemicals Targeting α-Synuclein Aggregation in Parkinson's Disease Models

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 9

Published: March 19, 2019

-Synuclein (-syn) is a presynaptic protein that regulates the release of neurotransmitters from synaptic vesicles in brain. -Syn aggregates, including Lewy bodies, are features both sporadic and familial forms Parkinson's disease (PD). These aggregates undergo several key stages fibrillation, oligomerization, aggregation. Therapeutic benefits drugs decline with progression offer only symptomatic treatment. This requires novel therapeutic strategies, which can either prevent or modify process. The link between -syn etiopathogenesis PD well established literature. Studies indicate an important target inhibition aggregation, fibrillation modification strategy. However, recent studies have shown plant extracts phytochemicals neuroprotective effects on oligomerization by targeting different its formation. Although many reviews antioxidant-mediated, effect symptoms been highlighted, antioxidant mechanisms show limited success for translation to clinical studies. identification specific α-syn aggregation will provide selective molecules develop new PD. present review provides overview summarizes observed underlying mechanisms. Furthermore, we synopsis current experimental models techniques used evaluate phytochemicals. Plant were found inhibit fibril formation oligomers. also appear direct oligomer into unstructured form promote nontoxic pathways suggested be valuable drug candidates related synucleinopathy. Current evidence vitro require confirmation vivo Further needed ascertain their potential safety preclinical pharmaceutical/nutritional development these dietary inclusion

Language: Английский

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Curcumol: From Plant Roots to Cancer Roots

International Journal of Biological Sciences, Journal Year: 2019, Volume and Issue: 15(8), P. 1600 - 1609

Published: Jan. 1, 2019

Natural products, an infinite treasure of bioactive scaffolds, have provided excellent reservoir for the discovery drugs since millennium.These naturally occurring, biologically active and therapeutically effective chemical entities emerged as novel paradigm prevention various diseases.This review aims to give update on sources well pharmacological profile curcumol, a pharmacologically sesquiterpenoid, which is imperative constituent several plants mainly from genus Curcuma.Curcumol has potential fight against cancer, oxidative stress, neurodegeneration, microbial infections, inflammation.Curcumol been documented potent inducer apoptosis in numerous cancer cells via targeting key signaling pathways MAPK/ERK, PI3K/Akt NF-κB are generally deregulated cancers.The reported data reveals multitarget activity curcumol treatment suggesting its importance anticancer drug future.It speculated that may provide opportunity cure but further investigations mechanism action preclinical trials still mandatory validate this natural killer therapies.

Language: Английский

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Role of Plant-Derived Flavonoids and Their Mechanism in Attenuation of Alzheimer’s and Parkinson’s Diseases: An Update of Recent Data

Molecules, Journal Year: 2018, Volume and Issue: 23(4), P. 814 - 814

Published: April 2, 2018

Neurodegeneration is a progressive loss of neuronal cells in certain regions the brain. Most neurodegenerative disorders (NDDs) share communal characteristic such as damage or reduction various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding more enthralling captivating suspend standstill pathology will be considered hallmark present times. Phytochemicals potential alternate synthetic line therapy against NDDs. review explores efficacy plant-derived flavonoids most common Alzheimer’s disease (AD) Parkinson’s (PD). Flavonoids biologically active phytochemicals which pharmacological effects, antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic anti-oxidant effects able attenuate through down-regulating nitric oxide (NO) production, by reducing tumor necrosis factor-α (TNF-α), excitotoxicity superoxide well acting tyrosine kinase (TK) monoamine oxidase (MAO) inhibiting enzyme.

Language: Английский

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Putative Roles of Plant-Derived Tannins in Neurodegenerative and Neuropsychiatry Disorders: An Updated Review

Molecules, Journal Year: 2019, Volume and Issue: 24(12), P. 2213 - 2213

Published: June 13, 2019

Neurodegenerative and neuropsychiatric diseases are characterized by the structural functional abnormalities of neurons in certain regions brain. These abnormalities, which can result progressive neuronal degeneration disability, incurable to date. Although comprehensive efforts have been made figure out effective therapies against these diseases, partial success has achieved complete recovery is still not a reality. At present, plants plant-derived compounds getting more attention because plethora pharmacological properties, they proving be better safer target as therapeutic interventions. This review aims highlight roles tannins, 'the polyphenol phytochemicals', tackling neurodegenerative including Alzheimer's Parkinson's well disorders like depression. Among multifarious properties anti-oxidative, anti-inflammatory, anti-cholinesterase activities emphasized terms neuroprotection. The current also throws light on mechanistic pathways various classes tannins execute neuroprotective effects. Despite their beneficial some harmful effects elaborated.

Language: Английский

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