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Biomolecules
Special Issues
Biomolecular Approaches and Drugs for Neurodegeneration
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Biomolecular Approaches and Drugs for Neurodegeneration

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 8952

Special Issue Editors

Dr. Giovanni N. Roviello

E-Mail Website
Guest Editor
Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Via P. Castellino 111, 80131 Naples, Italy
Interests: bioinorganic chemistry; synthetic chemistry; nucleic acid chemistry; spectroscopic studies; computational studies; environmental chemistry
Special Issues, Collections and Topics in MDPI journals
Dr. Caterina Vicidomini

E-Mail Website
Guest Editor
Istituto di Biostrutture e Bioimmagini IBB-CNR, Via Tommaso De Amicis 95, 80145 Naples, Italy
Interests: pharmaceutical chemistry; neurodrugs; protein interactions; spectroscopy; computational chemistry; phytochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neuropathies are very common and disabling neuropathies affecting the ever-growing aged population around the world, especially in Western countries. There is an urgent need to develop effective therapies for preventing or treating neuropathies. Protein/peptide aggregation is of fundamental importance in therapeutics because this type of event is related to pathologies of enormous social relevance, including neurodegeneration. Interestingly, G-quadruplex (G4) DNA and RNA structures are also related to several neuropathies, and ligands able to destabilize or modulate the aggregation of such nucleic acid secondary structures are therefore envisaged to work as neurodrugs. In this Special Issue, we wish to focus on the more recent experimental and theoretical approaches for neurodrug design and development, with particular attention paid to the mechanisms of drug interference with protein and peptide aggregation pathways; however, contributions on G4 nucleic acid–drug interaction, G4 targets in neurodegenerative diseases, and nucleopeptide chemistry are also welcome, as they could improve the overall knowledge on the aggregation-based biochemistry at the interface between neurodrug design and therapy. Other themes of interest are inherent the computational chemistry and machine learning applied to chemistry and biology in the context of neuropathology therapy. This Special Issue is open to the submission of both original articles and reviews that describe research and ideas on themes treated in this Special Issue for neurodegeneration-related molecular strategies.

Dr. Giovanni N. Roviello
Dr. Caterina Vicidomini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • proteins
  • peptides
  • amyloid
  • Alzheimer disease
  • Parkinson’s disease
  • neurodrugs
  • G-quadruplex nucleic acids
  • biotechnology
  • biomolecular targets
  • peptide aggregation
  • natural products
  • synthetic drugs
  • antiamyloid therapeutics
  • machine learning

Published Papers (5 papers)

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Research

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20 pages, 2583 KiB  
Article
A High-Throughput Screening of a Natural Products Library for Mitochondria Modulators
by Emmanuel Makinde, Linlin Ma, George D. Mellick and Yunjiang Feng
Biomolecules 2024, 14(4), 440; https://doi.org/10.3390/biom14040440 - 04 Apr 2024
Viewed by 568
Abstract
Mitochondria, the energy hubs of the cell, are progressively becoming attractive targets in the search for potent therapeutics against neurodegenerative diseases. The pivotal role of mitochondrial dysfunction in the pathogenesis of various diseases, including Parkinson’s disease (PD), underscores the urgency of discovering novel [...] Read more.
Mitochondria, the energy hubs of the cell, are progressively becoming attractive targets in the search for potent therapeutics against neurodegenerative diseases. The pivotal role of mitochondrial dysfunction in the pathogenesis of various diseases, including Parkinson’s disease (PD), underscores the urgency of discovering novel therapeutic strategies. Given the limitations associated with available treatments for mitochondrial dysfunction-associated diseases, the search for new potent alternatives has become imperative. In this report, we embarked on an extensive screening of 4224 fractions from 384 Australian marine organisms and plant samples to identify natural products with protective effects on mitochondria. Our initial screening using PD patient-sourced olfactory neurosphere-derived (hONS) cells with rotenone as a mitochondria stressor resulted in 108 promising fractions from 11 different biota. To further assess the potency and efficacy of these hits, the 11 biotas were subjected to a subsequent round of screening on human neuroblastoma (SH-SY5Y) cells, using 6-hydroxydopamine to induce mitochondrial stress, complemented by a mitochondrial membrane potential assay. This rigorous process yielded 35 active fractions from eight biotas. Advanced analysis using an orbit trap mass spectrophotometer facilitated the identification of the molecular constituents of the most active fraction from each of the eight biotas. This meticulous approach led to the discovery of 57 unique compounds, among which 12 were previously recognized for their mitoprotective effects. Our findings highlight the vast potential of natural products derived from Australian marine organisms and plants in the quest for innovative treatments targeting mitochondrial dysfunction in neurodegenerative diseases. Full article
(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration)
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18 pages, 6004 KiB  
Article
Neuroprotective Effects of the Nutraceutical Dehydrozingerone and Its C2-Symmetric Dimer in a Drosophila Model of Parkinson’s Disease
by Maria Dolores Setzu, Ignazia Mocci, Davide Fabbri, Paola Carta, Patrizia Muroni, Andrea Diana, Maria Antonietta Dettori and Maria Antonietta Casu
Biomolecules 2024, 14(3), 273; https://doi.org/10.3390/biom14030273 - 24 Feb 2024
Viewed by 1470
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons responsible for unintended or uncontrollable movements. Mutations in the leucine-rich repeat kinase 2 locus contribute to genetic forms of PD. The fruit fly Drosophila melanogaster carrying this mutation (LRRK2-Dm) [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons responsible for unintended or uncontrollable movements. Mutations in the leucine-rich repeat kinase 2 locus contribute to genetic forms of PD. The fruit fly Drosophila melanogaster carrying this mutation (LRRK2-Dm) is an in vivo model of PD that develops motor impairment and stands for an eligible non-mammalian paradigm to test novel therapeutic approaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger and presents anti-inflammatory, antioxidant and neuroprotective properties, making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1 mM for 14 and 21 days in the LRRK2-Dm, with the aim of assessing changes in rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-bars). The shorter treatment with both molecules revealed efficacy at the higher dose, improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-bars failure was observed with the DHZ-DIM. Our data indicate that the DHZ-DIM exerts a more potent neuroprotective effect with respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD. Full article
(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration)
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13 pages, 2604 KiB  
Article
Ladostigil Reduces the Adenoside Triphosphate/Lipopolysaccharide-Induced Secretion of Pro-Inflammatory Cytokines from Microglia and Modulate-Immune Regulators, TNFAIP3, and EGR1
by Fanny Reichert, Keren Zohar, Elyad Lezmi, Tsiona Eliyahu, Shlomo Rotshenker, Michal Linial and Marta Weinstock
Biomolecules 2024, 14(1), 112; https://doi.org/10.3390/biom14010112 - 16 Jan 2024
Viewed by 1040
Abstract
Treatment of aging rats for 6 months with ladostigil (1 mg/kg/day) prevented a decline in recognition and spatial memory and suppressed the overexpression of gene-encoding pro-inflammatory cytokines, TNFα, IL1β, and IL6 in the brain and microglial cultures. Primary cultures of mouse microglia stimulated [...] Read more.
Treatment of aging rats for 6 months with ladostigil (1 mg/kg/day) prevented a decline in recognition and spatial memory and suppressed the overexpression of gene-encoding pro-inflammatory cytokines, TNFα, IL1β, and IL6 in the brain and microglial cultures. Primary cultures of mouse microglia stimulated by lipopolysaccharides (LPS, 0.75 µg/mL) and benzoyl ATPs (BzATP) were used to determine the concentration of ladostigil that reduces the secretion of these cytokine proteins. Ladostigil (1 × 10−11 M), a concentration compatible with the blood of aging rats in, prevented memory decline and reduced secretion of IL1β and IL6 by ≈50%. RNA sequencing analysis showed that BzATP/LPS upregulated 25 genes, including early-growth response protein 1, (Egr1) which increased in the brain of subjects with neurodegenerative diseases. Ladostigil significantly decreased Egr1 gene expression and levels of the protein in the nucleus and increased TNF alpha-induced protein 3 (TNFaIP3), which suppresses cytokine release, in the microglial cytoplasm. Restoration of the aberrant signaling of these proteins in ATP/LPS-activated microglia in vivo might explain the prevention by ladostigil of the morphological and inflammatory changes in the brain of aging rats. Full article
(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration)
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Review

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29 pages, 2633 KiB  
Review
Therapeutic Strategies for Spinocerebellar Ataxia Type 1
by Laurie M. C. Kerkhof, Bart P. C. van de Warrenburg, Willeke M. C. van Roon-Mom and Ronald A. M. Buijsen
Biomolecules 2023, 13(5), 788; https://doi.org/10.3390/biom13050788 - 02 May 2023
Viewed by 4184
Abstract
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder that affects one or two individuals per 100,000. The disease is caused by an extended CAG repeat in exon 8 of the ATXN1 gene and is characterized mostly by a profound loss [...] Read more.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder that affects one or two individuals per 100,000. The disease is caused by an extended CAG repeat in exon 8 of the ATXN1 gene and is characterized mostly by a profound loss of cerebellar Purkinje cells, leading to disturbances in coordination, balance, and gait. At present, no curative treatment is available for SCA1. However, increasing knowledge on the cellular and molecular mechanisms of SCA1 has led the way towards several therapeutic strategies that can potentially slow disease progression. SCA1 therapeutics can be classified as genetic, pharmacological, and cell replacement therapies. These different therapeutic strategies target either the (mutant) ATXN1 RNA or the ataxin-1 protein, pathways that play an important role in downstream SCA1 disease mechanisms or which help restore cells that are lost due to SCA1 pathology. In this review, we will provide a summary of the different therapeutic strategies that are currently being investigated for SCA1. Full article
(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration)
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Other

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14 pages, 2979 KiB  
Systematic Review
A Systematic Review on Dementia and Translocator Protein (TSPO): When Nuclear Medicine Highlights an Underlying Expression
by Miriam Conte, Maria Silvia De Feo, Ferdinando Corica, Joana Gorica, Marko Magdi Abdou Sidrak, Flaminia De Cristofaro, Luca Filippi, Maria Ricci, Giuseppe De Vincentis and Viviana Frantellizzi
Biomolecules 2023, 13(4), 598; https://doi.org/10.3390/biom13040598 - 26 Mar 2023
Viewed by 1309
Abstract
Background: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation [...] Read more.
Background: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging. Methods: An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation. Results: A total of 50 articles was identified. Twelve papers were selected from the included studies’ bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment. Conclusion: Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of 18F makes this isotope a preferable choice to 11C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers’ effects and increasing the noise ratio in images. Full article
(This article belongs to the Special Issue Biomolecular Approaches and Drugs for Neurodegeneration)
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