Role of cell metabolism in the pathophysiology of brain size-associated neurodevelopmental disorders DOI Creative Commons
Lei Xing, Wieland Β. Huttner, Takashi Namba

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 199, P. 106607 - 106607

Published: July 17, 2024

Cell metabolism is a key regulator of human neocortex development and evolution. Several lines evidence indicate that alterations in neural stem/progenitor cell (NPC) lead to abnormal brain development, particularly size-associated neurodevelopmental disorders, such as microcephaly. Abnormal NPC causes impaired proliferation thus insufficient expansion NPCs for neurogenesis. Therefore, the production neurons, which major determinant size, decreased size brain, especially neocortex, significantly reduced. This review discusses recent progress understanding metabolism, focusing particular on glucose fatty acid amino (e.g., glutaminolysis serine metabolism). We provide an overview contributions these metabolic pathways evolution, well etiology disorders. Furthermore, we discuss advantages disadvantages various experimental models study developing brain.

Language: Английский

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection DOI
Shloka Negi, Sarah L. Stenton, Seth Berger

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme DOI Creative Commons

Markus C. B. Tecson,

Cyrina Joy Geluz,

Yolanda P. Cruz

et al.

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

Published: Jan. 22, 2025

Glutamine synthetase (GS) is a ubiquitous enzyme central to nitrogen metabolism, catalyzing the ATP-dependent formation of glutamine from glutamate and ammonia. Positioned at intersection metabolism with carbon activity GS subject sophisticated regulation. While intricate regulatory pathways that govern Escherichia coli were established long ago, recent work has demonstrated homologues are controlled by multiple distinct patterns, such as metabolite induced oligomeric state in archaeal 2-oxoglutarate. Such was enabled large part advances cryo-electron microscopy (cryoEM) allowed greater structural access this complex, assessment heterogeneous states protein-interactor-GS complexes. This perspective highlights understanding regulation, focusing on dynamic interplay between its state, binding, protein interactors. These interactions modulate activity, influencing cellular processes assimilation, stress responses. Furthermore, we explore emerging concept "moonlighting" functions, revealing roles palmitoylation, cell cycle ion channel modulation. diverse functions highlight newfound versatility beyond primary catalytic role suggest complex health disease warrant further study.

Language: Английский

Citations

1
Epigenetic and metabolic regulation of developmental timing in neocortex evolution DOI Creative Commons

Matilde Aquilino,

Nora Ditzer, Takashi Namba

et al.

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The human brain is characterized by impressive cognitive abilities. neocortex the seat of higher cognition, and expansion a hallmark evolution. While developmental programs are similar in different species, timing transitions capacity neural progenitor cells (NPCs) to proliferate differ, contributing increased production neurons during cortical development. Here, we review epigenetic regulation corticogenesis, focusing mostly on humans while building knowledge from studies mice. We discuss metabolic-epigenetic interplay as potential mechanism integrate extracellular signals into chromatin. Moreover, synthesize current understanding how metabolic deregulation can cause neurodevelopmental disorders. Finally, outline be investigated using organoid models.

Language: Английский

Citations

0
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection DOI Open Access
Shloka Negi, Sarah L. Stenton, Seth Berger

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Abstract More than 50% of families with suspected rare monogenic diseases remain unsolved after whole genome analysis by short read sequencing (SRS). Long-read (LRS) could help bridge this diagnostic gap capturing variants inaccessible to SRS, facilitating long-range mapping and phasing, providing haplotype-resolved methylation profiling. To evaluate LRS’s additional yield, we sequenced a disease cohort 98 samples, including 41 probands some family members, using nanopore sequencing, achieving per sample ∼36x average coverage 32 kilobase (kb) N50 from single flow cell. Our Napu pipeline generated assemblies, phased variants, calls. LRS covered, on average, coding exons in ∼280 genes ∼5 known Mendelian that were not covered SRS. In comparison detected rare, functionally annotated SVs tandem repeats, completely 87% protein-coding genes. de novo be used distinguish postzygotic mosaic prezygotic novos . Eleven solved, diverse underlying genetic causes compound heterozygous large-scale SVs, epigenetic modifications. study demonstrates potential enhance yield for diseases, implying utility future clinical genomics workflows.

Language: Английский

Citations

2
Role of cell metabolism in the pathophysiology of brain size-associated neurodevelopmental disorders DOI Creative Commons
Lei Xing, Wieland Β. Huttner, Takashi Namba

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 199, P. 106607 - 106607

Published: July 17, 2024

Cell metabolism is a key regulator of human neocortex development and evolution. Several lines evidence indicate that alterations in neural stem/progenitor cell (NPC) lead to abnormal brain development, particularly size-associated neurodevelopmental disorders, such as microcephaly. Abnormal NPC causes impaired proliferation thus insufficient expansion NPCs for neurogenesis. Therefore, the production neurons, which major determinant size, decreased size brain, especially neocortex, significantly reduced. This review discusses recent progress understanding metabolism, focusing particular on glucose fatty acid amino (e.g., glutaminolysis serine metabolism). We provide an overview contributions these metabolic pathways evolution, well etiology disorders. Furthermore, we discuss advantages disadvantages various experimental models study developing brain.

Language: Английский

Citations

1