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

Neurology International, Год журнала: 2025, Номер 17(2), С. 26 - 26

Опубликована: Фев. 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.

Язык: Английский

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Exploring the Efficacy and Safety of Nutritional Supplements in Alzheimer’s Disease

Nutrients, Год журнала: 2025, Номер 17(5), С. 922 - 922

Опубликована: Март 6, 2025

Background: Alzheimer's disease (AD) represents one of the major challenges modern medicine, with a growing impact on public health and healthcare systems. In recent years, dietary supplements use has been subject increasing interest as complementary strategy for prevention treatment disease. Materials Methods: A Review reviews was conducted following PRISMA guidelines REAPPRAISED checklist to evaluate efficacy safety supplement in AD. The search, performed across scientific databases, identified 54 relevant articles, including 53 mini-review, after applying specific inclusion criteria removing duplicates. Results: body evidence suggests that some may help reduce cognitive decline, inflammation, target mechanisms behind However, many these are still under investigation, mixed results highlighting need high-quality research. key challenge is lack data optimal dosages, administration duration, long-term safety, which limits clinical guidelines. Some studies have reported positive effects from regimens, such curcumin (800 mg/day), omega-3 fatty acids (2 g/day), resveratrol (600 mg/day). Other supplements, like phosphatidylserine (300 multinutrient formulations, probiotics, vitamin E (2000 IU/day), melatonin (3-10 also show benefits, though study variability makes conclusions uncertain. Conclusions: While certain potential mitigating decline AD, inconsistent findings gaps dosage highlight rigorous, large-scale trials. Future research should focus personalized, multimodal strategies integrating targeted supplementation, patterns, microbiota-gut-brain interactions enhanced neuroprotection.

Язык: Английский

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Paradoxical Boosting of Weak and Strong Spatial Memories by Hippocampal Dopamine Uncaging

eNeuro, Год журнала: 2024, Номер 11(5), С. ENEURO.0469 - 23.2024

Опубликована: Май 1, 2024

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release hippocampal CA1 region could modulate spatial memory formation. However, role of increase on weak or strong memories remains unclear. We show male mice exploring two objects located a familiar environment 5 min created short-term (weak) cannot be retrieved 1 d later, whereas 10 exploration long-term (strong) can later. Remarkably, elevation during encoding object location (OLMs) allowed their retrieval later but OLMs promoted preference over after 24 h. Moreover, uncaging did not have effect diminished location. Additionally, allow recovery and affect traces. Finally, increased theta oscillations, indicating promotes recurrent activation specific groups neurons. Our experiments demonstrate dopaminergic modulation depends strength hyperdopaminergic levels enhance experiences compromise normal storage memories.

Язык: Английский

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Entorhinal cortex–hippocampal circuit connectivity in health and disease

Frontiers in Human Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Сен. 20, 2024

The entorhinal cortex (EC) and hippocampal (HC) connectivity is the main source of episodic memory formation consolidation. entorhinal–hippocampal (EC-HC) connection classified as canonically glutamatergic and, more recently, has been characterized a non-canonical GABAergic connection. Recent evidence shows that both EC HC receive inputs from dopaminergic, cholinergic, noradrenergic projections modulate mnemonic processes linked to encoding consolidation memories. In present review, we address latest findings on EC-HC role neuromodulations during mechanisms memories highlight value cross-species approach unravel underlying cellular known. Furthermore, discuss how early neurodegeneration may contribute dysfunction observed in aging Alzheimer’s disease (AD). Finally, described exercise be fundamental tool prevent or decrease neurodegeneration.

Язык: Английский

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Photostimulation of Locus Coeruleus CA1 catecholaminergic terminals reversed spatial memory impairment in an Alzheimer's disease mouse model.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Rationale One of the earliest changes associated with Alzheimer's disease (AD) is loss catecholaminergic terminals in cortex and hippocampus originating from Locus Coeruleus (LC). This decline leads to reduced neurotransmitters hippocampus, affecting synaptic plasticity spatial memory. However, it unclear whether restoring transmission LC may alleviate memory deficits AD. Objectives study investigates how optogenetic stimulation projections locus coeruleus hippocampal CA1 region enhance disease. Methods We conducted experiments using a 12-month-old 3xTg-AD mouse model (AD-TH), which expresses Cre recombinase under control tyrosine hydroxylase (TH) gene. allowed us photostimulate before performing two different tasks inducing long-term potentiation (LTP). Results Optogenetic successfully reversed impairment retrieval aging AD-TH mice. Furthermore, this restored neurotransmitter levels enhanced plasticity, as demonstrated by an LTP protocol. Conclusions These findings indicate that circuitry (LC) plays crucial role disrupting contributing seen early stages highlights potential therapeutic benefits targeting neurons improve cognitive function patients

Язык: Английский

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Unscrambling the cellular and molecular threads of Neuroplasticity: Insights into Alzheimer’s disease pathogenesis

Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Neurotrophic factor alpha 1 gene therapy in Alzheimer’s disease: scope and advancements

Frontiers in Molecular Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Апрель 1, 2025

Alzheimer's disease (AD) is the leading cause of dementia, accounting for 60-80% all cases globally. Hallmark pathologies AD include accumulation amyloid β peptide and phosphorylated tau, to neuronal circuit dysfunction, defective axonal transport, neurotransmitter system (NTS) abnormalities. Disruptions in acetylcholine, GABA, dopamine, serotonin, glutamate levels, as well loss cholinergic, GABAergic, monoaminergic neurons, contribute progression AD. Additionally, neurotrophic factors like brain-derived factor (BDNF) nerve growth (NGF) are significantly reduced AD, impacting health synaptic integrity. This review highlights emerging role alpha 1 (NF-α1), also known carboxypeptidase E, NF-α1 shows neuroprotective neurogenesis-promoting properties, offering potential therapeutic interventions. The compares gene therapy with other neurotrophin-based treatments, providing insights into its efficacy management.

Язык: Английский

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Network Pharmacology-Guided Evaluation of Ginger and Cornelian Cherry Extracts Against Depression and Metabolic Dysfunction in Estrogen-Deficient Chronic Stressed Rats

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4829 - 4829

Опубликована: Май 18, 2025

This study investigated the therapeutic effects of water extracts from Zingiber officinale Roscoe (ginger) and Cornus officinalis Siebold Zucc. fruits (COF) on depression-like behavior metabolic dysfunction in estrogen-deficient rats exposed to chronic mild stress (CMS). Network pharmacology analysis identified three bioactive compounds ginger four COF, with 11 overlapping targets linked both depression pathways, primarily involving NR3C1, HTR2A, MAOA, SLC6A4 genes associated hypothalamic–pituitary–adrenal (HPA) axis regulation neurotransmitter modulation. Ovariectomized received 200 mg/kg/day or COF for 7 weeks, a 4-week CMS protocol initiated at week 3. Both significantly improved behaviors, memory performance, glucose tolerance, lipid profiles, bone mineral density, normalized HPA markers (corticosterone ACTH), increased hippocampal serotonin dopamine levels. Ginger demonstrated greater efficacy improving outcomes compared COF. Molecular docking further validated these findings, revealing strong stable interactions between key phytochemicals—such as hydroxygenkwanin telocinobufagin—and target proteins supporting their mechanistic role mood regulation. These results support supplementing promising botanical interventions estrogen-deficiency-related disorders, potential clinical application human-equivalent dose 1.5 g/day.

Язык: Английский

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Unveiling the Therapeutic Potential of Kelulut (Stingless Bee) Honey in Alzheimer’s Disease: Findings from a Rat Model Study

Antioxidants, Год журнала: 2024, Номер 13(8), С. 926 - 926

Опубликована: Июль 30, 2024

Alzheimer's disease (AD) poses a major worldwide health challenge because of its profound impact on cognitive abilities and overall well-being. Despite extensive research numerous clinical trials, therapeutic options remain limited. Our study aimed to investigate the potential Kelulut honey (KH) as novel agent for addressing multifactorial pathology AD. We tried evaluate disease-attenuating neuroprotective KH in intrahippocampally induced AD rat model by utilizing histochemistry enzyme-linked immunosorbent assay (ELISA) studies. A total 26 male Sprague Dawley rats weighing ~280-380 g were randomly divided into three groups: Control, AD-induced (Aβ), treated with (Aβ+KH). The latter two groups underwent stereotaxic surgery, where 6.25 µg amyloid β

Язык: Английский

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Exploring the Impact of Game Elements and Technological Platforms on Dementia Rehabilitation: A Scoping Review

International Journal of Human-Computer Interaction, Год журнала: 2024, Номер unknown, С. 1 - 22

Опубликована: Окт. 18, 2024

One effective strategy to improve the quality of life for people with dementia (PWD) is rehabilitation, though patients often show reluctance due disease's effects. A trending motivational approach gamification. However, most research in this field has focused on medical or technical aspects system development, less attention given role game elements patient experience. In study, a scoping review based PRISMA method was conducted gamified rehabilitation systems, focusing gamification elements, and interaction technological platforms. By reviewing 46 studies, we extracted pyramid, platforms, methods, compared them previous studies PWD interactions. This analysis identified opportunities challenges future research. Additionally, nine factors user experience design systems were presented results.

Язык: Английский

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