Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants DOI Creative Commons
Loïc Angrand, Jean-Daniel Masson, Alberto Rubio‐Casillas

et al.

Toxics, Journal Year: 2022, Volume and Issue: 10(9), P. 518 - 518

Published: Aug. 31, 2022

Autism spectrum disorder (ASD), schizophrenia, and bipolar are genetically complex heterogeneous neurodevelopmental disorders (NDDs) resulting from genetic factors gene-environment (GxE) interactions for which onset occurs in early brain development. Recent progress highlights the link between ASD (i) immunogenetics, neurodevelopment, inflammation, (ii) impairments of autophagy, a crucial process involved synaptic pruning. Among various environmental causing risk ASD, aluminum (Al)-containing vaccines injected during critical periods have received special attention triggered relevant scientific questions. The aim this review is to discuss current knowledge on role immune autophagy dysfunction as well preclinical studies question Al adjuvant impacts maturation. We highlight most recent breakthroughs lack epidemiological, pharmacokinetic pharmacodynamic data constituting "scientific gap". propose additional research, such that could contribute identify populations at risk, improving diagnosis, potentially development new therapeutic tools.

Language: Английский

Methods and applications for single-cell and spatial multi-omics DOI Open Access
Katy Vandereyken, Alejandro Sifrim, Bernard Thienpont

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(8), P. 494 - 515

Published: March 2, 2023

Language: Английский

Citations

626
New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications DOI Open Access
Ole A. Andreassen, Guy Hindley, Oleksandr Frei

et al.

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 4 - 24

Published: Jan. 14, 2023

Psychiatric genetics has made substantial progress in the last decade, providing new insights into genetic etiology of psychiatric disorders, and paving way for precision psychiatry, which individual profiles may be used to personalize risk assessment inform clinical decision‐making. Long recognized heritable, recent evidence shows that disorders are influenced by thousands variants acting together. Most these commonly occurring, meaning every a each disorder, from low high. A series large‐scale studies have discovered an increasing number common rare robustly associated with major disorders. The most convincing biological interpretation findings implicates altered synaptic function autism spectrum disorder schizophrenia. However, mechanistic understanding is still incomplete. In line their extensive epidemiological overlap, appear exist on continua share large degree one another. This provides further support notion current diagnoses do not represent distinct pathogenic entities, ongoing attempts reconceptualize nosology. also influences range behavioral somatic traits diseases, including brain structures, cognitive function, immunological phenotypes cardiovascular disease, suggesting shared potential importance. Current polygenic score tools, predict susceptibility illness, yet provide clinically actionable information. likely improve coming years, they eventually become part practice, stressing need educate clinicians patients about use misuse. review discusses key possible applications, suggests future directions.

Language: Английский

Citations

137
Genetics of human brain development DOI
Yi Zhou, Hongjun Song, Guo‐li Ming

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: Английский

Citations

72
A reference cell tree will serve science better than a reference cell atlas DOI Creative Commons
Silvia Domcke, Jay Shendure

Cell, Journal Year: 2023, Volume and Issue: 186(6), P. 1103 - 1114

Published: March 1, 2023

Language: Английский

Citations

68
Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy DOI Creative Commons
Théo Ribierre, Alexandre Bacq, Florian Donneger

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(6), P. 1125 - 1136

Published: May 6, 2024

Abstract Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy that necessitates neurosurgery. FCDII results from somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, which produce a subset dysmorphic cells clustered within healthy brain tissue. Here we show correlation between epileptiform activity acute slices obtained human surgical tissues and density neurons. We uncovered multiple signatures cellular senescence these pathological cells, including p53/p16 expression, SASP expression senescence-associated β-galactosidase activity. also administration senolytic drugs (dasatinib/quercetin) decreases load senescent reduces seizure frequency an Mtor S2215F preclinical mouse model, providing proof concept senotherapy may be useful approach control seizures. These findings pave way for therapeutic strategies selectively targeting mutated

Language: Английский

Citations

23
Cellular barcoding to decipher clonal dynamics in disease DOI
Vijay G. Sankaran, Jonathan S. Weissman, Leonard I. Zon

et al.

Science, Journal Year: 2022, Volume and Issue: 378(6616)

Published: Oct. 13, 2022

Cellular barcodes are distinct DNA sequences that enable one to track specific cells across time or space. Recent advances in our ability detect natural synthetic cellular barcodes, paired with single-cell readouts of cell state, have markedly increased knowledge clonal dynamics and genealogies the compose a variety tissues organs. These hold promise redefine view human disease. Here, we provide an overview barcoding approaches, discuss applications gain new insights into disease mechanisms, outlook on future applications. We unanticipated gained through studies cancer blood production describe how can be applied growing array medical fields, particularly increasing recognition contributions diseases.

Language: Английский

Citations

54
mTOR pathway: Insights into an established pathway for brain mosaicism in epilepsy DOI Creative Commons
А. В. Герасименко, Sara Baldassari, Stéphanie Baulac

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 182, P. 106144 - 106144

Published: May 4, 2023

The mechanistic target of rapamycin (mTOR) signaling pathway is an essential regulator numerous cellular activities such as metabolism, growth, proliferation, and survival. mTOR cascade recently emerged a critical player in the pathogenesis focal epilepsies cortical malformations. 'mTORopathies' comprise spectrum malformations that range from whole brain (megalencephaly) hemispheric (hemimegalencephaly) abnormalities to abnormalities, dysplasia type II (FCDII), which manifest with drug-resistant epilepsies. results somatic mutations activators AKT3, MTOR, PIK3CA, RHEB germline repressors, DEPDC5, NPRL2, NPRL3, TSC1 TSC2. mTORopathies are characterized by excessive activation, leading broad structural functional impairments. Here, we provide comprehensive literature review mTOR-activating linked epilepsy 292 patients discuss perspectives targeted therapeutics for personalized medicine.

Language: Английский

Citations

38
Latest clinical frontiers related to autism diagnostic strategies DOI Creative Commons
Samuele Cortese, Alessio Bellato, Alessandra Gabellone

et al.

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101916 - 101916

Published: Jan. 1, 2025

Language: Английский

Citations

1
The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders DOI
Bess Frost, Josh Dubnau

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 123 - 143

Published: April 25, 2024

Over 40% of the human genome is composed retrotransposons, DNA species that hold potential to replicate via an RNA intermediate and are evolutionarily related retroviruses. Retrotransposons most studied for their ability jump within a genome, which can cause damage novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, extrachromosomal circular DNAs, also be potent activators innate immune system. A growing body evidence suggests retrotransposons activated in age-related neurodegenerative disorders such activation causally contributes neurotoxicity. Here we provide overview retrotransposon biology outline disorders, with emphasis on those involving TAR-DNA binding protein-43 (TDP-43) tau. Studies date basis ongoing clinical trials promise innovative strategies ameliorate adverse effects dysregulation disorders.

Language: Английский

Citations

8
Principles of neural stem cell lineage progression: Insights from developing cerebral cortex DOI Creative Commons
Simon Hippenmeyer

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 79, P. 102695 - 102695

Published: Feb. 24, 2023

How to generate a brain of correct size and with appropriate cell-type diversity during development is major question in Neuroscience. In the developing neocortex, radial glial progenitor (RGP) cells are main neural stem that produce cortical excitatory projection neurons, cells, establish prospective postnatal cell niche lateral ventricles. RGPs follow tightly orchestrated developmental program when disrupted can result severe malformations such as microcephaly megalencephaly. The precise cellular molecular mechanisms instructing faithful RGP lineage progression however not well understood. This review will summarize recent conceptual advances contribute our understanding general principles progression.

Language: Английский

Citations

15