Neuronal Development and Disease: From Molecular Bases to Neurological Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 635

Special Issue Editor


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Guest Editor
1. Department of Medical Sciences Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal
2. Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal
Interests: synapse formation; local mRNA translation; local protein synthesis; neuronal cell death; excitotoxicity; neurodevelopmental disorders; microfluidics

Special Issue Information

Dear Colleague,

The intricate processes underlying neuronal development are critical in the establishment of a functional nervous system. From early neurogenesis to synaptic formation, these processes are finely tuned, allowing for the proper wiring and functioning of the brain. However, disruptions in these developmental pathways can lead to a wide array of neurological disorders, ranging from developmental disorders in childhood to neurodegenerative diseases in adulthood. Understanding the molecular, genetic, and cellular mechanisms that govern neuronal development and how these mechanisms are altered in disease is crucial in advancing therapeutic strategies.

This Special Issue on neuronal development and disease will bring together cutting-edge research that explores the intersection of these two key domains. Contributions from diverse areas, including stem cell biology, neurogenesis, synaptic plasticity, and neuroinflammation, will provide new insights into the developmental origins of neurological diseases. By including studies on topics spanning model organisms, advanced imaging techniques, and innovative therapeutic approaches, we aim to highlight the complexity of neuronal development and its disruption in disease contexts.

For this Special Issue, we welcome submissions of original research articles and reviews focusing on the mechanisms that explain the regular functioning of the nervous system, as wells as its functioning in disease states, at the cellular, system, or whole-organism level.

Dr. Ramiro Almeida
Guest Editor

Manuscript Submission Information

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Keywords

  • neuronal development
  • neurological disorders
  • neurogenesis
  • neuroinflammation
  • synaptic plasticity

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Published Papers (1 paper)

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Research

15 pages, 2592 KiB  
Article
Neuroprotection by Mitochondrial NAD Against Glutamate-Induced Excitotoxicity
by Bruna S. Paiva, Diogo Neves, Diogo Tomé, Filipa J. Costa, Inês C. Bruno, Diogo Trigo, Raquel M. Silva and Ramiro D. Almeida
Cells 2025, 14(8), 582; https://doi.org/10.3390/cells14080582 - 12 Apr 2025
Viewed by 482
Abstract
Excitotoxicity is a pathological process that occurs in many neurological diseases, such as stroke or epilepsy, and is characterized by the extracellular accumulation of high concentrations of glutamate or other excitatory amino acids (EAAs). Nicotinamide adenine dinucleotide (NAD) depletion is an early event [...] Read more.
Excitotoxicity is a pathological process that occurs in many neurological diseases, such as stroke or epilepsy, and is characterized by the extracellular accumulation of high concentrations of glutamate or other excitatory amino acids (EAAs). Nicotinamide adenine dinucleotide (NAD) depletion is an early event following excitotoxicity in many in vitro and in vivo excitotoxic-related models and contributes to the deregulation of energy homeostasis. However, the interplay between glutamate excitotoxicity and the NAD biosynthetic pathway is not fully understood. To address this question, we used a primary culture of rat cortical neurons and found that an excitotoxic glutamate insult alters the expression of the NAD biosynthetic enzymes. Additionally, using a fluorescent NAD mitochondrial sensor, we observed that glutamate induces a significant decrease in the mitochondrial NAD pool, which was reversed when exogenous NAD was added. We also show that exogenous NAD protects against the glutamate-induced decrease in mitochondrial membrane potential (MMP). Glutamate excitotoxicity changed mitochondrial retrograde transport in neurites, which seems to be reversed by NAD addition. Finally, we show that NAD and NAD precursors protect against glutamate-induced cell death. Together, our results demonstrate that glutamate-induced excitotoxicity acts by compromising the NAD biosynthetic pathway, particularly in the mitochondria. These results also uncover a potential role for mitochondrial NAD as a tool for central nervous system (CNS) regenerative therapies. Full article
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