Embryonic Striatal Grafting: Progress and Future Directions for Therapeutic Approaches to Neurodegenerative Diseases of the Basal Ganglia

Author(s):  
Fu-Chin Liu ◽  
Stephen B. Dunnett ◽  
Ann M. Graybiel
2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1030
Author(s):  
Julie Lake ◽  
Catherine S. Storm ◽  
Mary B. Makarious ◽  
Sara Bandres-Ciga

Neurodegenerative diseases are etiologically and clinically heterogeneous conditions, often reflecting a spectrum of disease rather than well-defined disorders. The underlying molecular complexity of these diseases has made the discovery and validation of useful biomarkers challenging. The search of characteristic genetic and transcriptomic indicators for preclinical disease diagnosis, prognosis, or subtyping is an area of ongoing effort and interest. The next generation of biomarker studies holds promise by implementing meaningful longitudinal and multi-modal approaches in large scale biobank and healthcare system scale datasets. This work will only be possible in an open science framework. This review summarizes the current state of genetic and transcriptomic biomarkers in Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, providing a comprehensive landscape of recent literature and future directions.


Author(s):  
Maria João Matos

Alzheimer's and Parkinson's disease are the most prevalent neurodegenerative diseases and the leading causes of dementia worldwide. The etiology of these multifactorial pathologies is not completely known. The available therapeutic approaches can cause temporary relief of symptoms but cannot slow down their progression or cure them. Life-changing therapeutic solutions are urgently needed, as the number of people suffering from these pathologies has been increasing quickly over the last few decades. Several targets are being studied, and innovative approaches are being pursued to find new therapeutic options. This overview is focused on the most recent information regarding the paradigm of using multitarget compounds to treat both Alzheimer's and Parkinson's disease.


2014 ◽  
Vol 43 ◽  
pp. 17-75 ◽  
Author(s):  
Nicolás Cuenca ◽  
Laura Fernández-Sánchez ◽  
Laura Campello ◽  
Victoria Maneu ◽  
Pedro De la Villa ◽  
...  

BioFactors ◽  
2016 ◽  
Vol 43 (6) ◽  
pp. 737-759 ◽  
Author(s):  
Seyedhossein Hekmatimoghaddam ◽  
Mohamad Reza Zare-Khormizi ◽  
Fatemeh Pourrajab

2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.


2020 ◽  
Vol 21 (2) ◽  
pp. 590 ◽  
Author(s):  
Mª Muñoz ◽  
Nerea de la Fuente ◽  
Amelia Sánchez-Capelo

γ-Aminobutiryc acid (GABA) is found extensively in different brain nuclei, including parts involved in Parkinson’s disease (PD), such as the basal ganglia and hippocampus. In PD and in different models of the disorder, an increase in GABA neurotransmission is observed and may promote bradykinesia or L-Dopa-induced side-effects. In addition, proteins involved in GABAA receptor (GABAAR) trafficking, such as GABARAP, Trak1 or PAELR, may participate in the aetiology of the disease. TGF-β/Smad3 signalling has been associated with several pathological features of PD, such as dopaminergic neurodegeneration; reduction of dopaminergic axons and dendrites; and α-synuclein aggregation. Moreover, TGF-β/Smad3 intracellular signalling was recently shown to modulate GABA neurotransmission in the context of parkinsonism and cognitive alterations. This review provides a summary of GABA neurotransmission and TGF-β signalling; their implications in PD; and the regulation of GABA neurotransmission by TGF-β/Smad3. There appear to be new possibilities to develop therapeutic approaches for the treatment of PD using GABA modulators.


2018 ◽  
Vol 175 (16) ◽  
pp. 3220-3229 ◽  
Author(s):  
Raquel L Arribas ◽  
Alejandro Romero ◽  
Javier Egea ◽  
Cristóbal de los Ríos

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