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Neuropharmacology and Neurodegenerative Diseases 2.0

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 August 2024 | Viewed by 1444

Special Issue Editor

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are devastating conditions for which a cure has not yet been defined since the mechanisms involved are still little understood. The incidence of neurodegenerative conditions, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, among the others, has increased in recent decades, associated with an aging population and significant cost. Nowadays, increased inflammation and oxidative stress are considered key modulators and common denominators of these pathologies.

Neuropharmacology has been evolving rapidly in order to identify new strategies that can support the nervous system, reducing the load of these disorders. The few treatments that are known and used are hampered by the Blood–Brain Barrier (BBB), which does not allow for the translocation of many therapeutic agents from blood to the brain, thus preventing the development of specific and innovative therapies. Basic research on this topic moves in two important directions:

  • On the one hand, towards the synthesis of newly engineered materials, such as nanomaterials, and towards the development of nano- and biotechnology that can develop sophisticated drug delivery systems. In this case, in fact, nanodrugs, with particles smaller than 100 nm, could elude the BBB;
  • On the other hand, natural products or derivatives of plants, with known anti-inflammatory and antioxidant properties, could be tested.

Dr. Jessica Maiuolo
Guest Editor

Manuscript Submission Information

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Keywords

  • neurodegenerative diseases
  • demyelinating diseases
  • blood–brain barrier
  • inflammation
  • reactive chemical species
  • mitochondria
  • endoplasmic reticulum
  • autophagy
  • apoptosis
  • nanodrugs
  • natural compounds
  • polyphenols

Published Papers (1 paper)

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Research

17 pages, 2881 KiB  
Article
Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells
by Jessica Maiuolo, Paola Costanzo, Mariorosario Masullo, Antonio D’Errico, Rosarita Nasso, Sonia Bonacci, Vincenzo Mollace, Manuela Oliverio and Rosaria Arcone
Int. J. Mol. Sci. 2023, 24(17), 13461; https://doi.org/10.3390/ijms241713461 - 30 Aug 2023
Cited by 3 | Viewed by 1194
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. Under normal conditions, beta-amyloid peptides exert important [...] Read more.
Alzheimer’s disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. Under normal conditions, beta-amyloid peptides exert important trophic and antioxidant roles, while their massive presence leads to a cascade of events culminating in the onset of AD. The fibrils of beta-amyloid proteins are formed by the process of fibrillogenesis that, starting from individual monomers of beta-amyloid, can generate polymers of this protein, constituting the hypothesis of the “amyloid cascade”. To date, due to the lack of pharmacological treatment for AD without toxic side effects, chemical research is directed towards the realization of hybrid compounds that can act as an adjuvant in the treatment of this neurodegenerative pathology. The hybrid compounds used in this work include moieties of a hydroxytyrosol, a nitrohydroxytyrosol, a tyrosol, and a homovanillyl alcohol bound to the N-benzylpiperidine moiety of donepezil, the main drug used in AD. Previous experiments have shown different properties of these hybrids, including low toxicity and antioxidant and chelating activities. The purpose of this work was to test the effects of hybrid compounds mixed with Aβ 1–40 to induce fibrillogenesis and mimic AD pathogenesis. This condition has been studied both in test tubes and by an in vitro model of neuronal differentiated human SH-SY5Y neuroblastoma cells. The results obtained from test tube experiments showed that some hybrids inhibit the activity of the enzymes AChE, BuChE, and BACE-1. Cell experiments suggested that hybrids could inhibit fibrillogenesis, negatively modulating caspase-3. They were also shown to exert antioxidant effects, and the acetylated hybrids were found to be more functional and efficient than nonacetylated forms. Full article
(This article belongs to the Special Issue Neuropharmacology and Neurodegenerative Diseases 2.0)
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