4.7 Review

Old and new challenges in Parkinson's disease therapeutics

期刊

PROGRESS IN NEUROBIOLOGY
卷 156, 期 -, 页码 69-89

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2017.04.006

关键词

Parkinson's disease; Pathophysiology; Cell therapy; Gene therapy; Molecular therapy; Clinical trials; Mesenchymal stromal/stem cells; Secretome

资金

  1. Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/ 33900/2009]
  2. IF development grant [IF/00111/2013]
  3. Northern Portugal Regional Operational Programme (NORTE) through European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]
  4. FEDER funds through Competitiveness Factors Operational Programme (COMPETE)
  5. National funds through Foundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038]
  6. Fundação para a Ciência e a Tecnologia [SFRH/BD/33900/2009] Funding Source: FCT

向作者/读者索取更多资源

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. (C) 2017 Elsevier Ltd. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Engineering, Biomedical

Enhanced neuronal differentiation by dynamic piezoelectric stimulation

Tiffany S. Pinho, Deolinda Silva, Jorge Cibrao Ribeiro, Ana Marote, Rui Lima, Salete J. Batista, Rita Melo, Clarisse Ribeiro, Cristiana B. Cunha, Irina S. Moreira, Senentxu Lanceros-Mendez, Antonio J. Salgado

Summary: This study focuses on the application of poled and coated PVDF films for neural differentiation and found that these films can induce neuronal differentiation under mechanical stimulation, which is further enhanced with a pre-coating step of poly-d-lysine and laminin.

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A (2023)

Article Clinical Neurology

Acute baclofen administration promotes functional recovery after spinal cord injury

Andreia G. Pinho, Susana Monteiro, Valentina Liberato, Diogo J. Santos, Jonas Campos, Jorge R. Cibra, Nuno A. Silva, Nidia de Sousa, Anton Barreiro-Iglesias, Antonio J. Salgado

Summary: This study aimed to understand the potential of baclofen as a treatment to promote recovery after spinal cord injury (SCI). The results showed that baclofen can improve locomotor and bladder function control in mice after SCI, and it may modulate the immune response. Although further research is needed to explore the mechanisms behind the functional improvements produced by baclofen, this study opens up new avenues for designing pharmacological strategies to promote SCI recovery.

SPINE JOURNAL (2023)

Review Cell Biology

Cell-based therapeutic strategies for treatment of spinocerebellar ataxias: an update

Joana Sofia Correia, Sara Duarte-Silva, Antonio Jose Salgado, Patricia Maciel

Summary: Spinocerebellar ataxias are heritable neurodegenerative diseases characterized by aggregation of mutant polyglutamine protein in neurons, causing dysfunction and death in the central nervous system. Stem cell transplantation has shown promise in pre-clinical trials for spinocerebellar ataxia types 1, 2, and 3, but the best route of administration and long-term effects are still uncertain. Further studies are needed to optimize cell type selection and delivery strategies, while considering the potential risks of repetitive transplantation. Despite challenges, cell-transplantation therapies have provided transient but beneficial outcomes in spinocerebellar ataxias.

NEURAL REGENERATION RESEARCH (2023)

Article Immunology

Secretomes derived from osteogenically differentiated jaw periosteal cells inhibit phenotypic and functional maturation of CD14+ monocyte-derived dendritic cells

Wanjing Cen, Felix Umrath, Antonio Jose Salgado, Siegmar Reinert, Dorothea Alexander

Summary: The secretomes derived from osteogenically induced jaw periosteum-derived mesenchymal stem cells (JPCs) have inhibitory effects on the maturation of monocyte-derived dendritic cells (MoDCs), as they reduce the formation of MoDC clusters and down-regulate the expression of CD80, CD86, and CD197 on MoDCs. The secretomes also enhance the uptake capacity of MoDCs and promote the expansion of regulatory T cells. Furthermore, the secretomes affect the gene expression of MoDCs, up-regulating CD209, HLA-DRA, CSF3, IL10, and IL8, and down-regulating IFN gamma and IL12B.

FRONTIERS IN IMMUNOLOGY (2023)

Article Cell Biology

StressMatic: A Novel Automated System to Induce Depressive- and Anxiety-like Phenotype in Rats

Joana Martins-Macedo, Antonio Mateus-Pinheiro, Catia Alves, Fernando Veloso, Eduardo D. Gomes, Ines Ribeiro, Joana S. Correia, Tiago Silveira-Rosa, Nuno D. Alves, Ana J. Rodrigues, Joao M. Bessa, Nuno Sousa, Joao F. Oliveira, Patricia Patricio, Luisa Pinto

Summary: This study developed an automated system for exposing rodents to a standard unpredictable chronic mild stress (uCMS) protocol. Comparing manual (uCMS) and automated (auCMS) stress-exposure protocols, the data showed similar impacts on behavioral and physiological measurements. This automated method represents a step forward in preclinical research with advantages in time and standardization.
Article Multidisciplinary Sciences

Spinal cord RNA-seq data after a baclofen treatment in mice with a spinal cord injury

Nidia de Sousa, Diego Robledo, Laura Gonzalez-Llera, Andreia G. Pinho, Diogo J. Santos, Susana Monteiro, Jonas Campos, Jorge R. Cibrao, Nuno A. Silva, Laura Sanchez, Antonio J. Salgado, Anton Barreiro-Iglesias

Summary: Spinal cord injury (SCI) has no available pharmacological treatments for promoting neurological recovery. Baclofen treatment has been shown to promote functional recovery in mice with compression SCI. This study provides transcriptomic data from adult mouse spinal cords collected 7 days after compression SCI and baclofen administration. The data includes raw RNA-seq data and bioinformatic analyses.

DATA IN BRIEF (2023)

Article Engineering, Biomedical

Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star-Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model

Deolinda Silva, Lucas Schirmer, Tiffany S. Pinho, Passant Atallah, Jorge R. Cibrao, Rui Lima, Joao Afonso, Sandra B-Antunes, Claudia R. Marques, Joao Dourado, Uwe Freudenberg, Rui A. Sousa, Carsten Werner, Antonio J. Salgado

Summary: Adipose tissue-derived stem cells (ASCs) secrete factors that promote regenerative mechanisms, such as axonal growth and inflammation reduction, leading to functional recovery in spinal cord injury (SCI) cases. However, systemic delivery may cause off-target effects, while local administration has low efficiency. This study presents a delivery system based on a hydrogel that continuously releases pro-regenerative cytokines and growth factors, inducing neural differentiation and improving motor function in SCI models.

ADVANCED HEALTHCARE MATERIALS (2023)

Review Cell Biology

Revolutionizing Disease Modeling: The Emergence of Organoids in Cellular Systems

Rita Silva-Pedrosa, Antonio Jose Salgado, Pedro Eduardo Ferreira

Summary: Cellular models offer opportunities to study human diseases, avoiding ethical restrictions and costs associated with animal models. iPSCs technology overcomes the complexities of hESCs and contributes to diagnosis, therapeutics, and regenerative medicine. 3D cell culture systems, like organoids, provide closer replication of cellular morphology and polarity, enabling the study of organ development, disease modeling, and drug discovery. Although organoids have limitations, they have become a powerful tool for understanding human physiology and the pathogenesis of various diseases.
Article Biochemistry & Molecular Biology

N-Acetylcysteine Treatment May Compensate Motor Impairments through Dopaminergic Transmission Modulation in a Striatal 6-Hydroxydopamine Parkinson's Disease Rat Model

Rita Caridade-Silva, Bruna Araujo, Joana Martins-Macedo, Fabio G. Teixeira

Summary: Preventing degeneration and the loss of dopaminergic neurons in Parkinson's Disease (PD) remains a challenge, and developing disease-modifying approaches is imperative. N-acetylcysteine (NAC) has shown promising potential in preserving the dopaminergic system and modulating PD mechanisms. In this study, NAC enhanced dopaminergic neuron viability and improved motor deficits in a rat model of PD, suggesting that it may serve as a modulator of PD degenerative mechanisms.

ANTIOXIDANTS (2023)

Review Cell & Tissue Engineering

Animal models in peripheral nerve transection studies: a systematic review on study design and outcomes assessment

Bruna Lopes, Andre Coelho, Rui Alvites, Ana Catarina Sousa, Patricia Sousa, Alicia Moreira, Luis Atayde, Antonio Salgado, Stefano Geuna, Ana Colette Mauricio

Summary: Animal models play a crucial role in peripheral nerve injury regeneration studies, but there is a lack of usage of large animal models. The application of large animal models needs to be expanded to improve translational medicine for clinical practice.

REGENERATIVE MEDICINE (2023)

Article Cell Biology

Astrocytes Undergo Metabolic Reprogramming in the Multiple Sclerosis Animal Model

Sofia Pereira das Neves, Joao Carlos Sousa, Ricardo Magalhaes, Fuying Gao, Giovanni Coppola, Sebatien Meriaux, Fawzi Boumezbeur, Nuno Sousa, Joao Jose Cerqueira, Fernanda Marques

Summary: Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Recent research has shown that reactive astrocytes in MS lesions undergo metabolic alterations and exhibit increased reactivity, potentially contributing to the progression of the disease.
Article Cell & Tissue Engineering

Cellular Aging Secretes: a Comparison of Bone-Marrow-Derived and Induced Mesenchymal Stem Cells and Their Secretome Over Long-Term Culture

Ana Marote, Diogo Santos, Barbara Mendes-Pinheiro, Claudia Serre-Miranda, Sandra Anjo, Joana Vieira, Filipa Ferreira-Antunes, Joana Sofia Correia, Caroline Borges-Pereira, Andreia G. Pinho, Jonas Campos, Bruno Manadas, Manuel R. Teixeira, Margarida Correia-Neves, Luisa Pinto, Pedro M. Costa, Laurent Roybon, Antonio J. Salgado

Summary: This study compared the secretomes of long-term cultured BM-MSCs and iMSCs, and conducted a comprehensive characterization of both sources. The results showed that although there were significant differences in proliferation between the two sources, the secretome composition of both sources was similar in pre-senescent and senescent states. These findings suggest that shifting from BM-MSCs to a more advantageous source like iMSCs may yield similar therapeutic effects as the gold-standard MSC source.

STEM CELL REVIEWS AND REPORTS (2023)

Meeting Abstract Cell & Tissue Engineering

FUNCTIONAL REGENERATION IN SPINAL CORD INJURY INDUCED BY THE SECRETOME OF ADIPOSE TISSUE DERIVED STEM CELLS

Jorge Ribeiro, Rita Silva, Susana Monteiro, Rui Lima, Sofia Serra, Fabio Teixeira, Jose Graca, Nuno Silva, Antonio Salgado

TISSUE ENGINEERING PART A (2022)

Meeting Abstract Cell & Tissue Engineering

DEVELOPMENT OF A STARPEG-HEPARIN HYDROGEL SYSTEM TO PROMOTE CONTROLLED AND SUSTAINED DELIVERY OF ADIPOSE TISSUE DERIVED STEM CELLS' SECRETOME FOR CNS REGENERATIVE MEDICINE

Deolinda Silva, Passant Atallah, Lucas Schirmer, Ayham Frra, Tiffany Santos Pinho, Antonio Jose Salgado, Carsten Werner

TISSUE ENGINEERING PART A (2022)

Meeting Abstract Cell & Tissue Engineering

DEVELOPING LIPID-BASED NANOPARTICLES FOR SYSTEMIC DELIVERY OF MESENCHYMAL STEM CELLS SECRETOME IN PARKINSON'S DISEASE

Sandra Barata-Antunes, Rui A. Sousa, Bruno F. B. Silva, Antonio J. Salgado

TISSUE ENGINEERING PART A (2022)

暂无数据