Beyond Antioxidant Effects: Nature-Based Templates Unveil New Strategies for Neurodegenerative Diseases

Bacci, Andrea; Runfola, Massimiliano; Sestito, Simona; Rapposelli, Simona

doi:10.3390/antiox10030367

Cited by 23Neurological Disorders and TreatmentsAlzheimer's disease research and treatmentsMedicinal Plants and Neuroprotection

Beyond Antioxidant Effects: Nature-Based Templates Unveil New Strategies for Neurodegenerative Diseases

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Bacci, Andrea, Runfola, Massimiliano, Sestito, Simona, Rapposelli, Simona·2021·Antioxidants

DOI 10.3390/antiox10030367PMC PMC7997428

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Abstract

The complex network of malfunctioning pathways occurring in the pathogenesis of neurodegenerative diseases (NDDs) represents a huge hurdle in the development of new effective drugs to be used in therapy. In this context, redox reactions act as crucial regulators in the maintenance of neuronal microenvironment homeostasis. Particularly, their imbalance results in the severe compromising of organism’s natural defense systems and subsequently, in the instauration of deleterious OS, that plays a fundamental role in the insurgence and progress of NDDs. Despite the huge efforts in drug discovery programs, the identification process of new therapeutic agents able to counteract the relentless progress of neurodegenerative processes has produced low or no effective therapies. Consequently, a paradigm-shift in the drug discovery approach for these diseases is gradually occurring, paving the way for innovative therapeutical approaches, such as polypharmacology. The aim of this review is to provide an overview of the main pharmacological features of most promising nature-based scaffolds for a possible application in drug discovery, especially for NDDs, highlighting their multifaceted effects against OS and neuronal disorders.

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Metallostasis can increase reactive oxygen species production, leading to an enhanced level of toxic radicals.
“However, metallostasis can increase ROS production leading to an enhanced level of toxic radicals [24].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [24]
Abnormal accumulation or altered trafficking of bio-metals, in particular copper, could lead to direct or indirect cellular damage.
“Abnormal accumulation or altered trafficking of bio-metals, in particular Cu, could lead to direct or indirect cellular damage.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [24]
Many studies revealed that metals could accelerate the cytotoxicity of misfolded protein aggregates.
“many studies revealed that metals could accelerate the cytotoxicity of misfolded protein aggregates.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [24]
In the brains of Alzheimer's disease patients, very high levels of copper, zinc, and iron ions have been observed, giving rise to the metal ion hypothesis.
“In the brains of AD patients, a very high level of these ions was instead observed, thus giving rise to the “metal ion hypothesis”.”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [24]
Metals can induce injury to biostructures such as proteins by interacting with specific structural regions and destabilizing their native conformation.
“Metals can induce injury to biostructures, such as proteins, interacting with some specific structural regions and destabilizing their native conformation”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [24]

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Research works printed but not linked: 1

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Polyphenols and neuroprotection: therapeutic implications for cognitive decline
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“Therefore, the conjunction with other pharmacophores, such as moiety belonging to an already in-use anti-AD drug, creates a new molecular entity possessing an endowed spectrum of activities [24].”
BackgroundSelf-citation

Authors: Bacci, A., Runfola, M., Sestito, S., & Rapposelli, S.
Affiliations: University of Pisa (IT)
University of Sassari (IT)
Corresponding author: Rapposelli, Simona
ORCID: Runfola, Massimiliano
Sestito, Simona
Rapposelli, Simona
Venue: Antioxidants
Publisher: MDPI AG
Published: 2021-02-28
Volume: 10
Issue: 3
Pages: 367
ISSN: 2076-3921 (ISSN-L)
DOI: 10.3390/antiox10030367
PMC: PMC7997428
OpenAlex: W3135358155
Cited by: 23
References: 174
Citations by year: 2026: 3 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 3
FWCI: 0.53
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Antioxidants (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Topics: Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords: neurodegenerative diseases, oxidative stress, redox regulation, drug discovery, polypharmacology, antioxidant activity, neuronal disorders, therapeutic agents

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Beyond Antioxidant Effects: Nature-Based Templates Unveil New Strategies for Neurodegenerative Diseases

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