Gene Co-Expression Network Analysis Implicates microRNA Processing in Parkinson's Disease Pathogenesis.

CONCLUSION: These results suggest that microRNA processing and function may play a role in the pathogenesis of PD, and thus may represent a useful target for future drug development. PMID: 30089309 [PubMed - as supplied by publisher]
Source: Neuro-Degenerative Diseases - Category: Neurology Authors: Tags: Neurodegener Dis Source Type: research

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Abstract Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by motor symptoms such as tremor, slowness of movement, rigidity, and postural instability, as well as non-motor features like sleep disturbances, loss of ability to smell, depression, constipation, and pain. Motor symptoms are caused by depletion of dopamine in the striatum due to the progressive loss of dopamine neurons in the substantia nigra pars compacta. Approximately 10% of PD cases are familial arising from genetic mutations in α-synuclein, LRRK2, DJ-1, PINK1, parkin, and several other proteins. The majority ...
Source: Current Protocols in Neuroscience - Category: Neuroscience Authors: Tags: Curr Protoc Neurosci Source Type: research
The Parkinson's Disease (PD)-associated gene leucine-rich repeat kinase (LRRK2) has been studied extensively in the brain. However, several studies have established that mutations in LRRK2 confer susceptibility to mycobacterial infection, suggesting LRRK2 also controls immunity. We demonstrate that loss of LRRK2 in macrophages induces elevated basal levels of type I interferons (IFN) and interferon stimulated genes (ISGs) and causes blunted interferon responses to mycobacterial pathogens and cytosolic nucleic acid agonists. Altered innate immune gene expression inLrrk2 knockout (KO) macrophages is driven by a combination o...
Source: eLife - Category: Biomedical Science Tags: Immunology and Inflammation Microbiology and Infectious Disease Source Type: research
Abstract The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of gr...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
Abstract Mitochondrial dysfunction is implicated in the pathogenesis of Parkinson's disease. Preliminary data have shown lower brain adenosine triphosphate (ATP) levels in Parkinson's disease versus age-matched healthy controls. Ursodeoxycholic acid (UDCA) may improve impaired mitochondrial function. Our objective was to evaluate UDCA tolerability, pharmacokinetics, and its effect on brain bioenergetics in individuals with Parkinson's disease. An open-label, prospective, multiple-ascending-dose study of oral UDCA in 5 individuals with Parkinson's disease was completed. A blood safety panel, plasma concentrations o...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research
I recently attended the 2020 Longevity Therapeutics conference in San Francisco. I presented on the work ongoing at Repair Biotechnologies, but as is usually the case the more important parts of the visit took place outside the bounds of the conference proper. Longevity Therapeutics is one of the four or five core conferences for the longevity industry, at which you'll meet many of the early participants - a mix of scientists, entrepreneurs, and investors, and patient advocates. As such, most of the conference goers have already seen my updates, or are otherwise aware of the Repair Biotechnologies programs aimed at thymic ...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Conclusion In this study, serum FGF-21, serum GDF-15, and blood mtDNA levels were similar in patients with PD and healthy controls and therefore unlikely to be satisfactory indicators of mitochondrial dysfunction in patients with PD. Classification of evidence This study provides Class III evidence that serum FGF-21, serum GDF-15, and blood mtDNA copy number levels do not distinguish patients with PD from healthy controls. There was no diagnostic uncertainty between patients with PD and healthy controls.
Source: Neurology Clinical Practice - Category: Neurology Authors: Tags: Mitochondrial disorders; see Genetics/Mitochondrial disorders, All Movement Disorders, Parkinson's disease/Parkinsonism, Class III, Mitochondrial disorders Research Source Type: research
Publication date: Available online 7 February 2020Source: Redox BiologyAuthor(s): Kondalarao Bankapalli, Vinaya Vishwanathan, Gautam Susarla, N. Sunayana, SreeDivya Saladi, Divya Peethambaram, Patrick D'SilvaAbstractMitochondria are indispensable organelles that perform critical cellular functions, including energy metabolism, neurotransmission, and synaptic maintenance. Mitochondrial dysfunction and impairment in the organellar homeostasis are key hallmarks implicated in the progression of neurodegenerative disorders. The members of DJ-1/ThiJ/PfpI family are highly conserved, and loss of DJ-1 (PARK7) function in humans re...
Source: Redox Biology - Category: Biology Source Type: research
Abstract Mutations in the human ATP13A2 gene are associated with an early-onset form of Parkinson's disease (PD) known as Kufor Rakeb Syndrome (KRS). Patients with KRS show increased iron deposition in the basal ganglia, suggesting iron toxicity-induced neurodegeneration as a potential pathogenesis associated with the ATP13A2 mutation. Previously we demonstrated that functional losses of ATP13A2 disrupt the lysosome's ability to store excess iron, leading to reduce survival of dopaminergic neuronal cells. To understand the possible mechanisms involved, we studied a Caenorhabditis elegans mutant defective in catp-6...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
AbstractLoss of dopaminergic neurons following Parkinson ’s disease (PD) diminishes quality of life in patients. The present study was carried out to investigate the protective effects of simultaneous inhibition of dipeptidyl peptidase-4 (DPP-4) and P2X7 purinoceptors in a PD model and explore possible mechanisms. The 6-hydroxydopamine (6-OHDA) was used as a tool to establish PD model in male Wister rats. The expressions of SIRT1, SIRT3, mTOR, PGC-1α, PTEN, P53 and DNA fragmentation were evaluated by ELISA assay. Behavioral impairments were determined using apomorphine-induced rotational and narrow beam tests. ...
Source: Metabolic Brain Disease - Category: Neurology Source Type: research
Conclusion: Together, proteomics approach both reveals novel molecular insights into αSyn-mediated neuroinflammation in PD and other synucleinopathies.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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