Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer’s and Parkinson’s Diseases

Neurology International, Journal Year: 2025, Volume and Issue: 17(2), P. 26 - 26

Published: Feb. 7, 2025

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates progressive permanent loss neurons major characteristic features these disorders. Although precise mechanisms causing disease (AD) (PD) still unknown, there is a wealth evidence suggesting that misfolded proteins, accumulation dysfunction neuroreceptors mitochondria, dysregulation enzymes, release neurotransmitters significantly influence pathophysiology diseases. There no effective protective medicine or therapy available even with availability numerous medications. an urgent need to create new powerful bioactive compounds since number people NDDs rising globally. Heterocyclic have consistently played pivotal role in drug discovery due their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine opicapone, feature heterocyclic cores. As therapeutic potential, heterocycles intriguing research topic for drugs PD AD. This review aims provide current insights into potential use targeting diverse targets manage potentially treat patients AD PD.

Language: Английский

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GSK-3β dysregulation in aging: Implications for tau pathology and Alzheimer's disease progression

Molecular and Cellular Neuroscience, Journal Year: 2025, Volume and Issue: unknown, P. 104005 - 104005

Published: March 1, 2025

Language: Английский

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Medium‐Chain Triglycerides Supplementation Protects Epilepsy‐Associated Behavioral Impairments in a Mouse Model

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(4)

Published: March 21, 2025

Presently there has been a growing interest in the development of dietary-based interventions as alternative therapies to combat chronic neurological conditions like epilepsy. Medium-chain triglycerides (MCT) are composed three fatty acids attached glycerol backbone and have shown several beneficial effects various diseases. The present study investigated MCT supplementation's impact on seizure severity associated neurobehavioral comorbidities pentylenetetrazole (PTZ) mouse kindling model. Mice were administered 35 mg/kg (i.p.) PTZ every other day for induction. kindled mice then subjected supplementation over 25 days with scoring at 5th following exposure. Behavioral analysis was initiated end supplementation. After that, lipid peroxidation assay, and, gene protein expression studies performed isolated hippocampus. significantly decreased scores compared control. treatment reduced immobility duration forced swim tail suspension tests, indicating reversal seizures-associated depression-like behavior. A significant reduction percentage spontaneous alternation observed control group T-maze test, which remained unchanged treated group. Furthermore, no change locomotion anxiety index supplemented In addition, attenuated altered hippocampal peroxidation, mRNA levels mTOR Gsk-3β. concluded that suppresses epileptic seizures behavior via interacting Gsk-3β signaling.

Language: Английский

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Targeting of PP2 A/GSK3β/PTEN Axis in Alzheimer Disease: The Mooting Evidence, Divine, and Devil

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: April 18, 2025

Abstract Alzheimer disease (AD) is a progressive neurodegenerative of the brain due to extracellular accumulation Aβ. In addition, intracellular hyperphosphorlyated tau protein which form neurofibrillary tangle (NFT) associated with neuronal injury and development AD. Aβ NFTs interact together induce inflammation oxidative stress further neurodegeneration in The exact relationship between tau, two proteins that accumulate within these lesions, has proven elusive. A growing body work supports notion may directly or indirectly accelerate formation. can adversely affect distinct molecular cellular pathways, thereby facilitating phosphorylation, aggregation, mislocalization, accumulation. drive pathology by activating specific kinases, providing straightforward mechanism enhance hyperphosphorylation NFT Many signaling pathways such as phosphatase 2A (PP2A), glycogen synthase kinase 3β (GSK3β), tensin homologue (PTEN) are intricate AD neuropathology. PP2A involved dephosphorylation deregulated AD, correlated cognitive impairment. PTEN critical regulator growth, survival, development, improving synaptic plasticity axonal regeneration. Nevertheless, mutated impairment inhibiting expression activity PP2A. Furthermore, dysregulation GSK3β affects Aβ, other pathogenesis Therefore, there close interaction among GSK3β, PTEN, exaggerates neuropathology activates PTEN. These findings specified related PP2A, modulation single component this axis not produce an effective effect against Modulation metformin statins reduce review aims discuss role GSK3β/PTEN/PP2A how targeting therapeutic strategy management conclusion, inhibition activation be more suitable than pathway. Metformin attenuate progression Graphical

Language: Английский

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Neuroprotective potential of hispidulin and diosmin: a review of molecular mechanisms

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(5)

Published: April 21, 2025

Language: Английский

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The Compelling Role of Brain‐Derived Neurotrophic Factor Signaling in Multiple Sclerosis: Role of BDNF Activators

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, acting as signal and neuromodulator in the central nervous system (CNS). BDNF synthesized from its precursor proBDNF within CNS peripheral tissues. Through activation of NTRK2/TRKB (neurotrophic receptor tyrosine kinase 2), promotes neuronal survival, synaptic plasticity, growth, whereas it inhibits microglial release pro-inflammatory cytokines. dysregulated different neurodegenerative diseases depressions. However, there major controversy concerning levels stages multiple sclerosis (MS). Therefore, this review discusses potential role signaling MS, how modulators affect pathogenesis outcomes disease.

Language: Английский

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Novel Compounds as NLRP3 Inhibitors for Treating Alzheimer’s Disease and Parkinson’s Disease

ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(8), P. 1203 - 1204

Published: July 29, 2024

Provided herein are novel compounds as NLRP3 inhibitors, pharmaceutical compositions, use of such in treating Alzheimer's disease and Parkinson's disease, processes for preparing compounds.

Language: Английский

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Exploring bacterial metabolites in microbe-human host dialogue and their therapeutic potential in Alzheimer’s diseases

Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Language: Английский

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Design, synthesis and biological evaluation of thieno[3,2-c]pyrazol-urea derivatives as potent glycogen synthase kinase 3β inhibitors based on the DFG-out conformation

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 112, P. 129932 - 129932

Published: Aug. 28, 2024

Language: Английский

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Role of Some Enzymes in Neurological Diseases

Published: June 10, 2024

Neurological diseases have a very serious impact on humanity. Major such as Alzheimer’s, Parkinson’s, Multiple Sclerosis, Epilepsy, Brain tumors, stroke, and Amyotrophic Lateral Sclerosis change the lives of many people significantly. Some these still do not complete treatment method. Enzymes take part in biological reactions catalysts are effective occurrence diseases. Important enzymes used neurological In this chapter, some important described.

Language: Английский

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