Exploring the potential of the ketogenic diet in autism spectrum disorder: metabolic, genetic, and therapeutic insights

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 8, 2025

Abstract Current treatment approaches for Autism spectrum disorder (ASD) primarily focus on symptom management rather than addressing underlying dysfunctions. The ketogenic diet (KD), a high-fat, low-carbohydrate inducing nutritional ketosis, has shown promise in treating epilepsy and may offer therapeutic benefits ASD by modulating metabolic neuroprotective pathways. This review examined the potential impact of KD mechanisms ASD. While evidence from human studies is limited, animal research large overlap modulated dysfunctions As such, targeting multiple disrupted pathways at once, presents multifaceted approach However, more needed effectiveness modulation Additionally, precision medicine could help identify individuals who would benefit most intervention, potentially extending its use to other psychiatric conditions with similar patterns. Consequently, interventions might show induce drastic paradigm shift understanding

Language: Английский

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Akt signaling pathway: a potential therapy for Alzheimer’s disease through glycogen synthase kinase 3 beta inhibition

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Journal Year: 2023, Volume and Issue: 59(1)

Published: Nov. 7, 2023

Abstract Alzheimer’s disease (AD) is a form of dementia marked by the accumulation neuritic plaques and neurofibrillary tangles through action GSK-3β with both significant epidemiological clinical impact. Current pharmacological treatment approaches are focused on symptomatic relief aims to suppress AD’s progression rather than modification. This issue has triggered further investigations about tau pathology as an important component in pathophysiology, one them being Akt signaling pathway. Based problem served AD, combined non-existence conclusive therapy for this disease; hence, study strives investigate potential therapeutical benefit towards AD. A total 82 studies included, consisting national international articles creating narrative review based PRISMA checklist. Variables searched study, include (AD), signaling, serine-9 phosphorylation, GSK-3β. Tau protein been mainstay physiopathology which largely influenced expression. shown inactivate phosphorylation. Thus, modulating optimizing pathway present encouraging prospects development innovative efficacious therapeutic strategies addressing Several have tried estimate harm well dose–effect relationship between concluding promising beneficial effect AD therapy. Here, we show effects theoretical empirical standpoints.

Language: Английский

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The multifaceted role of mitochondria in autism spectrum disorder

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

Published: Sept. 2, 2024

Abstract Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different disorders, including autism spectrum disorder (ASD), may have significant negative impact development and support functions. Mitochondrial dysfunction, manifested the abnormal activities electron transport chain impaired metabolism, greatly contributes ASD. The aberrant this organelle is such importance that ASD has been proposed as mitochondrial disease. It should be noted not only function In particular, these organelles are involved regulation Ca 2+ homeostasis, mechanisms programmed cell death, autophagy, reactive oxygen nitrogen species (ROS RNS) production. Several syndromes originated from mitochondria-related mutations display phenotype. Abnormalities handling ATP mitochondria affect synaptic transmission, plasticity, development, contributing ROS regulate activity permeability transition pore (mPTP). prolonged opening affects redox state mitochondria, impairs oxidative phosphorylation, activates apoptosis, ultimately leading death. A dysregulation between enhanced processes apoptosis inhibited autophagy leads accumulation toxic products brains individuals with Although many still investigated, whether they cause or consequence unknown, accumulating data show breakdown any functions contribute review, we discuss multifaceted role various aspects neuroscience.

Language: Английский

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Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer’s Disease, Parkinson’s Disease, and Autism Spectrum Disorder

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(7), P. 831 - 831

Published: June 25, 2024

Histamine performs dual roles as an immune regulator and a neurotransmitter in the mammalian brain. The histaminergic system plays vital role regulation of wakefulness, cognition, neuroinflammation, neurogenesis that are substantially disrupted various neurodegenerative neurodevelopmental disorders. H3 receptor (H3R) antagonists inverse agonists potentiate endogenous release brain histamine have been shown to enhance cognitive abilities animal models several Microglial activation subsequent neuroinflammation implicated impacting embryonic adult neurogenesis, contributing development Alzheimer's disease (AD), Parkinson's (PD), autism spectrum disorder (ASD). Acknowledging importance microglia both neurodevelopment, well their by histamine, offers intriguing therapeutic target for these inhibition H3Rs has found facilitate shift from proinflammatory M1 state anti-inflammatory M2 state, leading reduction activity microglial cells. Also, pharmacological studies demonstrated H3R showed positive effects reducing biomarkers, suggesting potential simultaneously modulating crucial neurotransmissions signaling cascades such PI3K/AKT/GSK-3β pathway. In this review, we highlight addressing pathology decline disorders, e.g., AD, PD, ASD, with inflammatory component.

Language: Английский

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Lipidomic profiling of mouse brain and human neuron cultures reveals a role for Mboat7 in mTOR-dependent neuronal migration

Science Translational Medicine, Journal Year: 2025, Volume and Issue: 17(779)

Published: Jan. 1, 2025

Mutations in lipid regulator genes are a frequent cause of autism spectrum disorder, including those regulating phosphatidylinositol (PI) and phosphoinositide 3-kinase signaling. MBOAT7 encodes key acyltransferase PI synthesis is mutated an autism-related condition with neurodevelopmental delay epilepsy. Using liquid chromatography–tandem mass spectrometry, we analyzed the PI-associated glycerolipidome mice humans during neurodevelopment found dynamic regulation at times corresponding to neural apoptosis brains Mboat7 knockout mice. function was necessary for polyunsaturated cortical migration, loss resulted massive accumulation precursor lysophosphatidylinositol hyperactive mTOR Inhibiting signaling rescued migration defects. Our findings demonstrate roles remodeling implicate neuronal revealing potential paths treatment deficiency.

Language: Английский

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Effects of sulforaphane on ABC and SRS scales in patients with autism spectrum disorder: a meta-analysis

Brain and Development, Journal Year: 2025, Volume and Issue: 47(2), P. 104321 - 104321

Published: Feb. 14, 2025

Language: Английский

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Unlocking the therapeutic potential of protein kinase inhibitors in neurodegenerative and psychiatric disorders

Published: Feb. 26, 2025

Protein phosphorylation is a fundamental regulatory mechanism governing broad spectrum of cellular processes. In the nervous system, it critical for modulating neurotransmitter release, synaptic plasticity, neuronal excitability, and cell survival. Dysregulation protein kinase activity closely linked to pathogenesis various neurological psychiatric disorders, positioning several kinases as promising therapeutic targets. Although inhibitors (PKIs), major class compounds that modulate activity, have shown considerable success in oncology, their application diseases remains early stages exploration. Of 82 PKIs approved by Food Drug Administration (FDA), 37 are now preclinical clinical trials conditions, primarily targeting signaling pathways mediated key implicated these diseases. This review examines roles effects neurodegenerative, psychiatric, selected such autism disorders (ASD) epilepsy. We focus on Abelson I (ABL1), calmodulin-dependent II (CaMKII), casein 1δ (CK1δ), c-Jun N-terminal (JNK), cyclin-dependent 5 (CDK5), dual-specificity tyrosine-phosphorylated regulated 1A (DYRK1A), leucine-rich repeat 2 (LRRK2), extracellular signal-regulated 1/2 (ERK1/2), glycogen synthase 3β (GSK3β), mammalian target rapamycin (mTOR), p38 mitogen-activated kinase, C (PKC) neurodegenerative Additionally, we discuss CaMKII, CDK5, ERK1/2, PI3K/AKT/GSK3, A (PKA), PKC focusing schizophrenia mood analyze GSK3β, mTOR ASD underscores potential while highlighting ongoing challenges need further research refine kinase-targeted therapies.

Language: Английский

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Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Highlights•Perturb-FISH combines spatial transcriptomics and readout of CRISPR perturbation•We recover the effects genetic perturbation on transcriptome single cells•We find specific networks related to cell neighbors in tissue•We connect time-resolved imaging phenotypes after perturbationSummaryPooled optical screens have enabled study cellular interactions, morphology, or dynamics at massive scale, but they not yet leveraged power highly plexed single-cell resolved transcriptomic readouts inform molecular pathways. Here, we present a combination with parallel detection situ amplified guide RNAs (Perturb-FISH). Perturb-FISH recovers intracellular that are consistent RNA-sequencing-based (Perturb-seq) screen lipopolysaccharide response cultured monocytes, it uncovers intercellular density-dependent regulation innate immune response. Similarly, three-dimensional xenograft models, identifies tumor-immune interactions altered by knockout. When paired functional separate autism spectrum disorder risk genes human-induced pluripotent stem (hIPSC) astrocytes, shows common calcium activity their associated dysregulated is thus general method for studying associations biology resolution.Graphical abstract

Language: Английский

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Journal Year: 2023, Volume and Issue: 13(5), P. 816 - 816

Published: May 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Language: Английский

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Language: Английский

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