scholarly journals Therapeutic Approaches to Dysphagia Treatment in Parkinson Disease: A Review

2019 ◽  
Vol 6 (4) ◽  
Author(s):  
Ali Akbar Dashtelei ◽  
Ahmad Reza Khatoonabadi ◽  
Jalal Bakhtiari
Keyword(s):  
Parkinson Disease ◽  
Therapeutic Approaches ◽  
Dysphagia Treatment

scholarly journals PIAS2-mediated blockade of IFN-β signaling: a basis for sporadic Parkinson disease dementia

2021 ◽  
Author(s):  
Joana Magalhaes ◽  
Emilie Tresse ◽  
Patrick Ejlerskov ◽  
Erling Hu ◽  
Yawei Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson Disease ◽  
Cognitive Impairments ◽  
Meta Analysis ◽  
Ectopic Expression ◽  
Therapeutic Approaches ◽  
Mitochondrial Homeostasis ◽  
New Therapeutic Approaches ◽  
P53 Signaling ◽  
Dopaminergic Neuron Loss

AbstractFamilial Parkinson disease (PD) is associated with rare genetic mutations, but the etiology in most patients with sporadic (s)PD is largely unknown, and the basis for its progression to dementia (sPDD) is poorly characterized. We have identified that loss of IFNβ or IFNAR1, the receptor for IFNα/β, causes pathological and behavioral changes resembling PDD, prompting us to hypothesize that dysregulated genes in IFNβ-IFNAR signaling pathway predispose one to sPD. By transcriptomic analysis, we found defective neuronal IFNβ-IFNAR signaling, including particularly elevated PIAS2 associated with sPDD. With meta-analysis of GWASs, we identified sequence variants in IFNβ-IFNAR-related genes in sPD patients. Furthermore, sPDD patients expressed higher levels of PIAS2 mRNA and protein in neurons. To determine its function in brain, we overexpressed PIAS2 under a neuronal promoter, alone or with human α-synuclein, in the brains of mice, which caused motor and cognitive impairments and correlated with intraneuronal phosphorylated (p)α-synuclein accumulation and dopaminergic neuron loss. Ectopic expression of neuronal PIAS2 blocked mitophagy, increased the accumulation of senescent mitochondrial and oxidative stress, as evidenced by excessive oxDJ1 and 8OHdG, by inactivating ERK1/2-P53 signaling. Conversely, PIAS2 knockdown rescued the clinicopathological manifestations of PDD in Ifnb–/– mice on restoring mitochondrial homeostasis, oxidative stress, and pERK1/2-pP53 signaling. The regulation of JAK-STAT2-PIAS2 signaling was crucial for neurite outgrowth and neuronal survival and excitability and thus might prevent cognitive impairments. Our findings provide insights into the progression of sPD and dementia and have implications for new therapeutic approaches.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

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.

Lessons From the Neural Bases of Speech and Voice

2011 ◽  
Vol 21 (1) ◽  
pp. 5-14
Author(s):  
Christy L. Ludlow
Keyword(s):  
Brain Networks ◽  
Neural Substrates ◽  
Voice Behavior ◽  
Therapeutic Approaches ◽  
Neural Bases ◽  
Sound Foundation ◽  
The Brain ◽  
Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

Physiologic Studies Provide New Perspectives on Early Speech Development

2010 ◽  
Vol 20 (2) ◽  
pp. 29-36
Author(s):  
Erin M. Wilson ◽  
Ignatius S. B. Nip
Keyword(s):  
Motor Control ◽  
Motor Development ◽  
Motion Tracking ◽  
Speech Development ◽  
Speech Motor Control ◽  
Therapeutic Approaches ◽  
Facial Motion ◽  
Disordered Speech ◽  
Speech Motor ◽  
Physiologic Data

Abstract Although certain speech development milestones are readily observable, the developmental course of speech motor control is largely unknown. However, recent advances in facial motion tracking systems have been used to investigate articulator movements in children and the findings from these studies are being used to further our understanding of the physiologic basis of typical and disordered speech development. Physiologic work has revealed that the emergence of speech is highly dependent on the lack of flexibility in the early oromotor system. It also has been determined that the progression of speech motor development is non-linear, a finding that has motivated researchers to investigate how variables such as oromotor control, cognition, and linguistic factors affect speech development in the form of catalysts and constraints. Physiologic data are also being used to determine if non-speech oromotor behaviors play a role in the development of speech. This improved understanding of the physiology underlying speech, as well as the factors influencing its progression, helps inform our understanding of speech motor control in children with disordered speech and provide a framework for theory-driven therapeutic approaches to treatment.

Popliteal entrapment syndrome and age

VASA ◽  
2012 ◽  
Vol 41 (4) ◽  
pp. 262-268 ◽  
Author(s):  
Schweizer ◽  
Hügli ◽  
Koella ◽  
Jeanneret
Keyword(s):  
Risk Factors ◽  
Leg Pain ◽  
Walking Distance ◽  
Therapeutic Approaches ◽  
Long Distance ◽  
Entrapment Syndrome ◽  
Long Distance Running ◽  
Popliteal Entrapment ◽  
Popliteal Entrapment Syndrome ◽  
Atherosclerotic Risk Factors

On the occasion of diagnosing a popliteal entrapment syndrome in a 59-year old man with no cardiovascular risk factors, who developed acute ischemic leg pain during long distance running, we give an overview on this entity with emphasis on patients’age. The different types of the popliteal artery compression syndrome are summarized. The diagnostic and therapeutic approaches are discussed. The most important clinical sign of a popliteal entrapment syndrome is the lack of atherosclerotic risk factors in patients with limited walking distance. Not only in young athletes but also in patients more than 50 years old the popliteal entrapment syndrome has to be taken into account.

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