Journal of neural transmission
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Meta Analysis
Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of Parkinson's disease.
Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor (CCR2) on the susceptibility of Parkinson's disease (PD) have reported inconsistent results. Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two gene polymorphisms and PD risk. We performed a meta-analysis of five eligible studies to summarize the data describing the association between PD risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. ⋯ However, CCR2 V64I polymorphism is not correlated with PD risk. The results should be interpreted with caution due to limited sample and heterogeneity. Large scale and well-designed studies are needed to validate our findings.
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The prevalence of Parkinson's disease, which affects millions of people worldwide, is increasing due to the aging population. In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson's disease encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson's disease progression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicity and clinical safety tests for new indications, can be used to identify treatment compounds. ⋯ In this review, we discuss the multiple effects and clinical properties of tetracyclines and their potential use in Parkinson's disease treatment. In addition, we examine the hypothesis that the anti-inflammatory activities of tetracyclines regulate inflammasome signaling. Based on their excellent safety profiles in humans from their use for over 50 years as antibiotics, we propose the repurposing of tetracyclines, a multitarget antibiotic, to treat Parkinson's disease.
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Cholinergic signaling plays a key role in regulating striatal function. The principal source of acetylcholine in the striatum is the cholinergic interneurons which, although low in number, densely arborize to modulate striatal neurotransmission. This modulation occurs via strategically positioned nicotinic and muscarinic acetylcholine receptors that influence striatal dopamine, GABA and other neurotransmitter release. ⋯ This altered cholinergic signaling is an important contributor to Parkinson's disease as well as to the dyskinesias that develop with L-dopa therapy, the gold standard for treatment. Indeed, multiple preclinical studies show that cholinergic receptor drugs may be beneficial for the treatment of L-dopa-induced dyskinesias. In this review, we discuss the evidence indicating that therapeutic modulation of the cholinergic system, particularly targeting of nicotinic cholinergic receptors, may offer a novel approach to manage this debilitating side effect of dopamine replacement therapy for Parkinson's disease.
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Review
Dementia with Lewy bodies and Parkinson's disease-dementia: current concepts and controversies.
Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although sharing many clinical, neurochemical and morphological features, according to DSM-5, are two entities of major neurocognitive disorders with Lewy bodies of unknown etiology. Despite considerable clinical overlap, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia often preceding parkinsonism in DLB and onset of cognitive impairment after onset of motor symptoms in PDD. Both are characterized morphologically by widespread cortical and subcortical α-synuclein/Lewy body plus β-amyloid and tau pathologies. ⋯ In view of the controversies about the nosology and pathogenesis of both syndromes, there remains a pressing need to differentiate them more clearly and to understand the processes leading these synucleinopathies to cause one disorder or the other. Clinical management of both disorders includes cholinesterase inhibitors, other pharmacologic and nonpharmacologic strategies, but these have only a mild symptomatic effect. Currently, no disease-modifying therapies are available.
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Review
Cognitive deficits in adults with obstructive sleep apnea compared to children and adolescents.
Obstructive sleep apnea (OSA) can negatively affect the patient's physical and psychological functioning, as well as their quality of life. A major consequence of OSA is impaired cognitive functioning. Indeed, several studies have shown that OSA mainly leads to deficits in executive functions, attention, and memory. ⋯ We found that deficits in working memory, attention, or executive functions cognitive domains are found in both adults and children with OSA. However, children with OSA also show changes in behavior and phonological processing necessary for proper development. Moreover, we examine the possible OSA treatments in children and adults that can have a positive influence on cognition, and therefore, improve patients' general functioning and quality of life.