Novel Therapeutic Approaches for Neurodegenerative Diseases Treatment, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (10 November 2023) | Viewed by 4072

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Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autónoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
Interests: bioactive compounds; cell signaling; drug delivery; drug discovery; enzymology; high-throughput screening; metalloproteases; molecular pharmacology; nanoparticles; neuropeptides; neurodegenerative diseases; parkinson's disease; protein-protein interaction inhibitors; protein engineering; protein structure; protease inhibitors; protein folding and aggregation; substrate specificity; X-ray crystallography
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Dear Colleagues,

Neurodegenerative disorders are typically characterized by the progressive loss of specific populations of neurons in the brain. They can be classified according to a variety of primary clinical features and are associated with characteristic molecular abnormalities. The most common neurodegenerative disorders are amyloidoses, tauopathies, α-synucleinopathies, and TDP-43 proteinopathies. Nearly all of these disorders are associated with the accumulation of protein deposits and with alterations in normal proteostasis. Despite recent advances in the field, most of the molecular mechanisms involved in disease progression are not completely understood. However, since protein aggregation is a central event in neurological disorders, a variety of novel approaches have been focused on developing novel pharmacologically active molecules targeting this process. In addition, our understanding of amyloid structures has been boosted by recent advances in the field of structural biology and cryo-EM; these advances have facilitated the recent elucidation of a large number of high-resolution amyloid structures associated with neurodegeneration. Without a doubt, such ground-breaking discoveries will facilitate the structure-based design of novel, functional, and specific protein aggregation inhibitors. Additionally, there is an increasing focus on the utilization of nanomaterials as efficient drug delivery systems targeting neurodegenerative disorders.

The focus of this Special Issue is on the development and identification of novel molecules and therapeutic approaches dedicated to treating neurodegenerative diseases. The topics include (but are not limited to) the following: the design and development of novel protein-aggregation inhibitors; drug delivery using nanotechnology; and the development and characterization of pharmacologically active compounds targeting proteostasis and neurodegeneration.

Dr. Javier Garcia-Pardo
Guest Editor

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Keywords

  • neurodegenerative diseases
  • structure of amyloid fibrils
  • protein aggregation
  • Parkinson’s disease
  • amyloidoses
  • α-synucleinopathies
  • tauopathies
  • TDP-43 proteinopathies
  • cell signaling
  • drug discovery
  • drug delivery
  • nanotechnology
  • high-throughput screening
  • aggregation inhibitor
  • protease inhibitor
  • proteostasis

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Published Papers (2 papers)

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Review

23 pages, 1191 KiB  
Review
Advanced Progress in the Role of Adipose-Derived Mesenchymal Stromal/Stem Cells in the Application of Central Nervous System Disorders
by Haiyue Wu, Yishu Fan and Mengqi Zhang
Pharmaceutics 2023, 15(11), 2637; https://doi.org/10.3390/pharmaceutics15112637 - 16 Nov 2023
Cited by 7 | Viewed by 1976
Abstract
Currently, adipose-derived mesenchymal stromal/stem cells (ADMSCs) are recognized as a highly promising material for stem cell therapy due to their accessibility and safety. Given the frequently irreversible damage to neural cells associated with CNS disorders, ADMSC-related therapy, which primarily encompasses ADMSC transplantation and [...] Read more.
Currently, adipose-derived mesenchymal stromal/stem cells (ADMSCs) are recognized as a highly promising material for stem cell therapy due to their accessibility and safety. Given the frequently irreversible damage to neural cells associated with CNS disorders, ADMSC-related therapy, which primarily encompasses ADMSC transplantation and injection with exosomes derived from ADMSCs or secretome, has the capability to inhibit inflammatory response and neuronal apoptosis, promote neural regeneration, as well as modulate immune responses, holding potential as a comprehensive approach to treat CNS disorders and improve prognosis. Empirical evidence from both experiments and clinical trials convincingly demonstrates the satisfactory safety and efficacy of ADMSC-related therapies. This review provides a systematic summary of the role of ADMSCs in the treatment of central nervous system (CNS) disorders and explores their therapeutic potential for clinical application. ADMSC-related therapy offers a promising avenue to mitigate damage and enhance neurological function in central nervous system (CNS) disorders. However, further research is necessary to establish the safety and efficacy of clinical ADMSC-based therapy, optimize targeting accuracy, and refine delivery approaches for practical applications. Full article
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30 pages, 2535 KiB  
Review
Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools
by Paula Moyano, Emma Sola, María Victoria Naval, Lucia Guerra-Menéndez, Maria De la Cabeza Fernández and Javier del Pino
Pharmaceutics 2023, 15(8), 2048; https://doi.org/10.3390/pharmaceutics15082048 - 30 Jul 2023
Cited by 2 | Viewed by 1664
Abstract
Environmental pollutants’ (EPs) amount and diversity have increased in recent years due to anthropogenic activity. Several neurodegenerative diseases (NDs) are theorized to be related to EPs, as their incidence has increased in a similar way to human EPs exposure and they reproduce the [...] Read more.
Environmental pollutants’ (EPs) amount and diversity have increased in recent years due to anthropogenic activity. Several neurodegenerative diseases (NDs) are theorized to be related to EPs, as their incidence has increased in a similar way to human EPs exposure and they reproduce the main ND hallmarks. EPs induce several neurotoxic effects, including accumulation and gradual deposition of misfolded toxic proteins, producing neuronal malfunction and cell death. Cells possess different mechanisms to eliminate these toxic proteins, including heat shock proteins (HSPs) and the proteasome system. The accumulation and deleterious effects of toxic proteins are induced through HSPs and disruption of proteasome proteins’ homeostatic function by exposure to EPs. A therapeutic approach has been proposed to reduce accumulation of toxic proteins through treatment with recombinant HSPs/proteasome or the use of compounds that increase their expression or activity. Our aim is to review the current literature on NDs related to EP exposure and their relationship with the disruption of the proteasome system and HSPs, as well as to discuss the toxic effects of dysfunction of HSPs and proteasome and the contradictory effects described in the literature. Lastly, we cover the therapeutic use of developed drugs and recombinant proteasome/HSPs to eliminate toxic proteins and prevent/treat EP-induced neurodegeneration. Full article
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