An exciting and relevant topic is addressed in this paper collection encompassing both peripheral and central nervous system mechanisms of damage. This is of particular interest since neurons are a perennial cell population and, therefore, neurotoxicity understanding and management is a relevant challenge to treat/prevent neurological disorders [,,]. There are many different potentially neurotoxic agents which include chemotherapy drugs, environmental pollution, et cetera. Mechanisms of damage that involve the peripheral and/or central nervous system are explored to pave the way to potential treatment strategies relying on a robust biological rational.
Since neurons are excitable cells, ion channels/transporters can be a pivotal element leading to axonal damage and neuronal death [,]. A clear-cut review of their involvement, exploiting as a playground chemotherapy-induced peripheral neurotoxicity (CIPN) is provided as well as an in depth reasoning on how ion channels/transporters are quire susceptible, in their functioning, to changes in the environment the cell is exposed to which can be also triggering neurotoxicity.
The central nervous system is not overlooked too in this paper collection, as mentioned above, and the role of excitotoxicity [,] is also dissected in the in depth in the neurodegenerative disorder and in pain modulation.
Another topic that is presented via research data is the role of oxidative stress in determining alterations of the nervous system [,,,], exploiting zebrafish models, as well as its role in determining neurotoxicity acting against glial cells.
Last, but not least, our Special Issue is enriched by a detailed review of mechanisms leading to an entity that is becoming more and more relevant: HIV-associated neurocognitive disorder (HAND) [,].
Author Contributions
Writing—original draft preparation, P.A.; writing—review and editing, E.P. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Conflicts of Interest
The authors declare no conflicts of interest.
References
- Libertini, G.; Ferrara, N. Aging of Perennial Cells and Organ Parts According to the Programmed Aging Paradigm. Age 2016, 38, 35. [Google Scholar] [CrossRef] [PubMed]
- Cserép, C.; Pósfai, B.; Dénes, Á. Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions. Neuron 2021, 109, 222–240. [Google Scholar] [CrossRef] [PubMed]
- Magrassi, L.; Leto, K.; Rossi, F. Lifespan of Neurons Is Uncoupled from Organismal Lifespan. Proc. Natl. Acad. Sci. USA 2013, 110, 4374–4379. [Google Scholar] [CrossRef] [PubMed]
- Harris, K.; Won, S.J.; Uruk, G.; Mai, N.; Ogut, D.; Zhao, Y.; Xie, L.; Baxter, P.; Everaerts, K.; Sah, R.; et al. Excitotoxic Neuronal Death Requires Superoxide Entry into Neurons through Volume-Regulated Anion Channels. Sci. Adv. 2025, 11, eadw0424. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Jin, W.; Zhou, H.; Wang, X.; Ren, H.; Yang, X.; Luo, K.; Dou, X. Role of Mitochondrial Ca2+ in Stroke: From Molecular Mechanism to Treatment Strategy (Review). Mol. Med. Rep. 2025, 32, 271. [Google Scholar] [CrossRef] [PubMed]
- Wu, W.L.; Gong, X.X.; Qin, Z.H.; Wang, Y. Molecular Mechanisms of Excitotoxicity and Their Relevance to the Pathogenesis of Neurodegenerative Diseases-an Update. Acta Pharmacol. Sin. 2025. [Google Scholar] [CrossRef] [PubMed]
- Dong, X.X.; Wang, Y.; Qin, Z.H. Molecular Mechanisms of Excitotoxicity and Their Relevance to Pathogenesis of Neurodegenerative Diseases. Acta Pharmacol. Sin. 2009, 30, 379–387. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.W.; Choi, H.; Hwang, U.K.; Kang, J.C.; Kang, Y.J.; Kim, K.I.; Kim, J.H. Toxic Effects of Lead Exposure on Bioaccumulation, Oxidative Stress, Neurotoxicity, and Immune Responses in Fish: A Review. Environ. Toxicol. Pharmacol. 2019, 68, 101–108. [Google Scholar] [CrossRef] [PubMed]
- Kumar, V.; Gill, K.D. Oxidative Stress and Mitochondrial Dysfunction in Aluminium Neurotoxicity and Its Amelioration: A Review. Neurotoxicology 2014, 41, 154–166. [Google Scholar] [CrossRef] [PubMed]
- Prakash, C.; Soni, M.; Kumar, V. Mitochondrial Oxidative Stress and Dysfunction in Arsenic Neurotoxicity: A Review. J. Appl. Toxicol. 2016, 36, 179–188. [Google Scholar] [CrossRef] [PubMed]
- Ma, Y.; Su, Q.; Yue, C.; Zou, H.; Zhu, J.; Zhao, H.; Song, R.; Liu, Z. The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity. Int. J. Mol. Sci. 2022, 23, 13491. [Google Scholar] [CrossRef] [PubMed]
- Eggers, C.; Arendt, G.; Hahn, K.; Husstedt, I.W.; Maschke, M.; Neuen-Jacob, E.; Obermann, M.; Rosenkranz, T.; Schielke, E.; Straube, E. HIV-1-Associated Neurocognitive Disorder: Epidemiology, Pathogenesis, Diagnosis, and Treatment. J. Neurol. 2017, 264, 1715–1727. [Google Scholar] [CrossRef] [PubMed]
- Clifford, D.B. HIV-Associated Neurocognitive Disorder. Curr. Opin. Infect. Dis. 2017, 30, 117–122. [Google Scholar] [CrossRef] [PubMed]
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