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Molecular Mechanisms of Neurological and Psychiatric Disease, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 2143

Special Issue Editors


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Guest Editor
1. Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy
2. Department of Human Sciences, Faculty of Humanities Educations and Sports, Pegaso University, 80143 Naples, Italy
Interests: pathophysiology; movement disorders; motor memory; motor dysfunction; synaptic plasticity; brain circuitry; basal ganglia; striatum (putamen); medium spiny neurons; mitochondria; neurologic and phychiatric disorders; protein synthesis
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Santa Lucia Foundation, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy
2. Faculty of Medicine and Surgery, Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy
Interests: operative; neuroscience

Special Issue Information

Dear Colleagues,

Until several decades ago, psychological and behavioural interventions were the primary treatments for mental health disorders.

Thanks to modern psychopharmacology, medications are accepted to treat more psychiatric disorders.

Unfortunately, the mechanism behind many medications is unknown. Several therapeutic approaches are derived from neurological pathologies.

Psychiatric disorders are often present in various neurological diseases like Alzheimer's and Parkinson's disease, epilepsy, migraine, essential tremors, and stroke. Depression, anxiety disorders, and cognitive impairment are the most common comorbid diagnoses in neurological diseases. It is important to note that comorbidities are frequently overlooked due to common neurochemical mechanisms or a loss of previous functioning levels.

Moreover, some medications may have drawbacks, including drug interactions, side effects, and low effectiveness. In light of these, evidence has become essential to characterize the molecular mechanism of neurological and psychiatric disease to ensure the best treatments are utilized.

The colossal effort of researchers to increase the knowledge of many psychiatric and neurological disorders in the last few decades has helped us to understand not only the developmental stages of many diseases but, principally, the mechanism of action of medication on specific molecular targets.

This Special Issue aims to collect original research articles (regular and rapid communication) and reviews on the underlying molecular mechanisms of psychiatric and degenerative diseases and the therapeutic properties of substances, including those derived from plants.

Dr. Giuseppina Martella
Dr. Maria Meringolo
Guest Editors

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Keywords

  • Alzheimer's and Parkinson's diseases
  • epilepsy
  • migraine
  • essential tremors
  • stroke
  • depression
  • anxiety disorders
  • cognitive impairment

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Published Papers (2 papers)

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Review

46 pages, 2889 KB  
Review
Neuronutrition and Nrf2 Brain Resilience Signaling: Epigenomics and Metabolomics for Personalized Medicine in Nervous System Disorders from Bench to Clinic
by Maria Concetta Scuto, Carmelina Daniela Anfuso, Cinzia Lombardo, Eleonora Di Fatta, Raffaele Ferri, Nicolò Musso, Giulia Zerbo, Morena Terrana, Miroslava Majzúnová, Gabriella Lupo and Angela Trovato Salinaro
Int. J. Mol. Sci. 2025, 26(19), 9391; https://doi.org/10.3390/ijms26199391 - 25 Sep 2025
Viewed by 638
Abstract
Neuronutrition to improve brain resilience to stress and human health has received considerable attention. The use of specific nutrients is effective in preventing and slowing neurodegenerative and neuropsychiatric disorders. Selective neuronutrients, including polyphenols, short-chain fatty acids (SCFAs), tryptophan, tyrosine, and sulfur metabolites, can [...] Read more.
Neuronutrition to improve brain resilience to stress and human health has received considerable attention. The use of specific nutrients is effective in preventing and slowing neurodegenerative and neuropsychiatric disorders. Selective neuronutrients, including polyphenols, short-chain fatty acids (SCFAs), tryptophan, tyrosine, and sulfur metabolites, can modulate the dysregulated nuclear factor erythroid 2 (Nrf2) pathway through neuroepigenetic modifications and altered levels of neurotransmitters such as serotonin, melatonin, and dopamine. In particular, abnormal epigenetic alterations in the promoter function of the NFE2L2/Nrf2 gene may contribute to the onset and progression of various diseases by disrupting cellular homeostasis. Recent evidence has documented that polyphenols are capable of modulating Nrf2 signaling; to do this, they must reverse hypermethylation in the CpG islands of the NFE2L2 gene. This process is achieved by modifying the activity of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Furthermore, a diverse group of polyphenolic metabolites can be identified and quantified using innovative mass spectrometry platforms in both in vitro models and human urine samples to investigate redox metabolic homeostasis under physiological and pathophysiological conditions. This review aims to deepen the current understanding of the role of nutrient-derived secondary metabolites. It highlights innovative strategies to effectively prevent, slow, or potentially reverse neuroinflammation and oxidative stress, key drivers of neuronal damage. The targeted application of these metabolites can be considered a novel, personalized neuronutritional approach to promote brain health and neuronal adaptation. Full article
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23 pages, 1936 KB  
Review
Neuroprotective Potential of Major Alkaloids from Nelumbo nucifera (Lotus): Mechanisms and Therapeutic Implications
by Douyang Zhao, Linlin Ma, Jeremy Brownlie, Kathryn Tonissen, Yang Pan and Yunjiang Feng
Int. J. Mol. Sci. 2025, 26(17), 8280; https://doi.org/10.3390/ijms26178280 - 26 Aug 2025
Viewed by 1204
Abstract
Nelumbo nucifera (lotus) has long been used in traditional medicine across Asia, and its bioactive alkaloids have recently garnered attention for their neuroprotective properties. This review summarizes the current research on the mechanisms by which lotus-derived alkaloids, particularly neferine, nuciferine, liensinine, and isoliensinine, [...] Read more.
Nelumbo nucifera (lotus) has long been used in traditional medicine across Asia, and its bioactive alkaloids have recently garnered attention for their neuroprotective properties. This review summarizes the current research on the mechanisms by which lotus-derived alkaloids, particularly neferine, nuciferine, liensinine, and isoliensinine, protect neural tissues. These compounds exhibit a wide range of pharmacological activities, including antioxidant and anti-inflammatory effects, regulation of calcium signaling and ion channels, promotion of neurogenesis, and modulation of key neurotransmitter systems, such as dopaminergic, cholinergic, and GABAergic pathways. Notably, they attenuate tau hyperphosphorylation, reduce oxidative stress-induced neuronal apoptosis, and enhance neurotrophic signaling via BDNF-related pathways. While antioxidant and anti-inflammatory actions are the most extensively studied, emerging evidence also highlights their roles in autophagy modulation and mitochondrial protection. Together, these findings suggest that lotus alkaloids are promising candidates for the prevention and treatment of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Further investigation is warranted to explore the synergistic mechanisms and potential clinical applications of these compounds. Full article
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