Acta Tropica, Год журнала: 2024, Номер unknown, С. 107494 - 107494
Опубликована: Дек. 1, 2024
Язык: Английский
Seminars in Nuclear Medicine, Год журнала: 2024, Номер 54(4), С. 622 - 633
Опубликована: Март 13, 2024
Язык: Английский
Процитировано
23
Molecules, Год журнала: 2024, Номер 29(9), С. 2127 - 2127
Опубликована: Май 3, 2024
Neurodegeneration is a gradual decay process leading to the depletion of neurons in both central and peripheral nervous systems, ultimately resulting cognitive dysfunctions deterioration brain functions, alongside decline motor skills behavioral capabilities. Neurodegenerative disorders (NDs) impose substantial socio-economic strain on society, aggravated by advancing age world population absence effective remedies, predicting negative future. In this context, urgency discovering viable therapies critical and, despite significant efforts medicinal chemists developing potential drug candidates exploring various small molecules as therapeutics, regrettably, truly treatment yet be found. Nitrogen heterocyclic compounds, particularly those containing indole nucleus, which has emerged privileged scaffold, have attracted particular attention for variety pharmacological applications. This review analyzes rational design strategy adopted different research groups development anti-neurodegenerative indole-based compounds modulate molecular targets involved NDs, with reference most recent advances between 2018 2023.
Язык: Английский
Процитировано
18
European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 267, С. 116195 - 116195
Опубликована: Янв. 29, 2024
Язык: Английский
Процитировано
13
NeuroMarkers., Год журнала: 2025, Номер 2(2), С. 100041 - 100041
Опубликована: Март 8, 2025
Язык: Английский
Процитировано
1
Materials Today Bio, Год журнала: 2023, Номер 21, С. 100701 - 100701
Опубликована: Июнь 17, 2023
Alzheimer's disease (AD) is a type of dementia that affects vast number people around the world, causing great deal misery and death. Evidence reveals relationship between presence soluble Aβ peptide aggregates severity in patients. The BBB (Blood Brain Barrier) key problem because it prevents therapeutics from reaching desired places. To address issue, lipid nanosystems have been employed to deliver therapeutic chemicals for anti-AD therapy precise targeted manner. applicability clinical significance (Galantamine, Nicotinamide, Quercetin, Resveratrol, Curcumin, HUPA, Rapamycin, Ibuprofen) will be discussed this review. Furthermore, implications aforementioned compounds treatment examined. Thus, review pave way researchers fashion therodiagnostics approaches based on nanomedicine overcome problems delivering molecules across blood brain barrier (BBB).
Язык: Английский
Процитировано
19
ACS Omega, Год журнала: 2025, Номер 10(6), С. 5148 - 5171
Опубликована: Фев. 3, 2025
Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative affecting mostly the elderly population. The main pathological features of AD are extracellular Aβ plaques generated by APP cleavage through amyloidogenic pathway, intracellular neurofibrillary tangles (NFT) resulting from hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, actual causes unknown, but several studies suggest hereditary mutations in PSEN1 -2, APOE4, APP, TAU genes major perpetrators. In order to understand etiology pathogenesis AD, various hypotheses proposed. These include following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, deficiency, gut dysbiosis. Currently approved therapeutic interventions donepezil, galantamine, rivastigmine, which cholinesterase inhibitors (ChEIs), memantine, N-methyl-d-aspartate (NMDA) antagonist. treatment strategies focus on only symptomatic management attenuating symptoms not regeneration neurons or clearance Tau. This review focuses pathophysiology, novel targets, disease-altering treatments such as α-secretase modulators, active immunotherapy, passive natural antioxidant products, nanomaterials, antiamyloid therapy, aggregation inhibitors, transplantation fecal microbiota stem cells, microtubule stabilizers that clinical trials still under investigation.
Язык: Английский
Процитировано
1
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13302 - 13302
Опубликована: Дек. 11, 2024
This review aims to address the significant challenges of treating central nervous system (CNS) disorders such as neurodegenerative diseases, strokes, spinal cord injuries, and brain tumors. These are difficult manage due complexity disease mechanisms protective blood–brain barrier (BBB), which restricts drug delivery. Recent advancements in nanoparticle (NP) technologies offer promising solutions, with potential applications delivery, neuroprotection, neuroregeneration. By examining current research, we explore how NPs can cross BBB, deliver medications directly targeted CNS regions, enhance both diagnostics treatment. Key NP strategies, passive targeting, receptor-mediated transport, stimuli-responsive systems, demonstrate encouraging results. Studies show that may improve minimize side effects, increase therapeutic effectiveness models Alzheimer’s, Parkinson’s, stroke, glioblastoma. thus represent a approach for disorder management, combining delivery diagnostic capabilities enable more precise effective treatments could significantly benefit patient outcomes.
Язык: Английский
Процитировано
6
Advanced Science, Год журнала: 2023, Номер 11(1)
Опубликована: Ноя. 21, 2023
Abstract Histone deacetylase 6 (HDAC6) is one of the key histone deacetylases (HDACs) that regulates various cellular functions including clearance misfolded protein and immunological responses. Considerable evidence suggests HDAC6 closely related to amyloid tau pathology, two primary hallmarks Alzheimer's disease (AD). It still unclear whether expression changes with deposition in AD during progression or may be regulating phagocytosis neuroinflammation other neuropathological AD. In this work, pathological accumulation brains over age as well relationship its regulatory activity ‐ pathogenesis pathophysiological alterations aimed enlightened using newly developed inhibitor (HDAC6i) PB118 microglia BV2 cell 3D‐AD human neural culture model. Results suggest structure‐based rational design led biologically compelling HDAC6i multiple mechanisms clear Aβ deposits by upregulating phagocytosis, improve tubulin/microtubule network enhancing acetyl α‐tubulin levels, regulate different cytokines chemokines responsible for inflammation, significantly reduce phospho‐tau (p‐tau) levels associated These findings indicate plays roles pathophysiology potentially serves a suitable pharmacological target through chemical biology‐based drug discovery
Язык: Английский
Процитировано
13
RSC Pharmaceutics, Год журнала: 2024, Номер 1(2), С. 161 - 181
Опубликована: Янв. 1, 2024
This review mainly highlights the use of polymer–drug conjugates as an advanced drug delivery system to improve treatment AD and other neurodegenerative diseases.
Язык: Английский
Процитировано
4
ACS Omega, Год журнала: 2024, Номер 9(12), С. 13556 - 13591
Опубликована: Март 11, 2024
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia that rapidly becoming a major health problem, especially in developed countries because their increasing life expectancy. Two main problems are often associated with disease: (i) absence widely accessible "gold-standard" for early diagnosis and (ii) lack effective therapies disease-modifying effects. The recent success monoclonal antibody lecanemab played an important role not only clarifying possible druggable pathway but also spelling revival small molecule drug discovery. Unlike bulky biologics, molecules structurally less complex, generally cheaper, compatible at-home oral consumption, making it feasible people to start regimen stay on longer. In this sense, small-molecule near-infrared fluorescent theranostics have been gaining more attention from scientific community, as they potential simultaneously provide diagnostic outputs deliver therapeutic action, paving way toward personalized medicine AD patients. They shift "status-quo" expensive limited-access PET radiotracers inexpensive handy imaging tools available primary patient screening preclinical animal studies. Herein, we review advances field disease, detailing design strategies, synthetic approaches properties vitro vivo. With Review, intend milestone acquired knowledge theranostics, encouraging future development properly designed theranostic compounds improved chances reach clinical applications.
Язык: Английский
Процитировано
3