Neuroscience
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Randomized Controlled Trial Controlled Clinical Trial
Transcranial Magnetic Stimulation and H1-Magnetic Resonance Spectroscopy Measures of Excitation and Inhibition Following Lorazepam Administration.
This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABAA receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. ⋯ Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA.
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Tau is a microtubule-associated protein that serves as a promoter of microtubule assembly and stability in neuron cells. In a collective group of neurodegenerative diseases called tauopathies, tau processing is altered as a result of gene mutations and post-translational modifications. In particular, in Alzheimer's disease (AD) or AD-like conditions, tau becomes hyperphosphorylated and forms toxic aggregates inside the cell. ⋯ In particular, a few of these co-chaperones, such as FK506-binding protein (FKBP) 51, protein phosphatase (PP) 5, cell division cycle 37 (Cdc37), and S100A1 have family members that are reported to affect Hsp90-mediated tau processing in either a similar or an opposite manner. Here, we provide a holistic review of these selected co-chaperones and their family proteins and introduce a novel Hsp90-binding Cdc37 relative, Cdc37-like-1 (Cdc37L1 or L1) in tau regulation. Overall, the proteins discussed here highlight the importance of studying family proteins in order to fully understand the mechanism of tau pathogenesis and to establish drug targets for the treatment of tauopathies.
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Parkinson's disease (PD) is a common neurodegenerative disease with movement disorders including resting tremor, bradykinesia, rigidity, and postural instability. The key pathological features of PD are selective loss of dopaminergic (DA) neurons in substantial nigra and the presence of Lewy bodies (LBs). Mutations in TMEM230 (transmembrane protein 230) have been recently reported to play a pathological role and contribute to PD pathogenesis. ⋯ R141L, p.*184Wext*5, p.*184PGext*5). TMEM230-linked PD cases exhibit late-onset, good-response to levodopa, and typical clinical features of sporadic PD with DA neuronal loss in substantial nigra and Lewy body pathology. In this mini review, we recap the current literature of TMEM230 in genetic, neurobiological, and pathological studies in order to further understand the potential roles of TMEM230 in PD pathogenesis.
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CD36 is a membrane protein with wide distribution in the human body, is enriched in the monocyte-macrophage system and endothelial cells, and is involved in the cellular uptake of long chain fatty acids (LCFA) and oxidized low-density lipoproteins. It is also a scavenger receptor, binding hydrophobic amyloid fibrils found in the Alzheimer's disease (AD) brain. In neurobiology research, it has been mostly studied in relationship with chronic ischemia and stroke, but it was also related to amyloid clearance by microglial phagocytosis. ⋯ The balance of the two approaches, centered on microglia, is poorly understood. Furthermore, CD36 evaluation in AD clinical studies is still at a very early stage and there is a gap in the knowledge regarding the impact of LCFA on AD progression and CD36 expression and genetic phenotype. This review summarizes the role played by CD36 in the pathogenic amyloid cascade and explore the translatability of preclinical data towards clinical research.
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Parkinson's disease (PD) is a prevalent age-related neurodegenerative disorder that results in the progressive impairment of motor and cognitive functions. The majority of PD cases are sporadic, and only 5% of patients are associated with mutations in a few genes, which cause the early onset or familial PD. ⋯ In the last decade, genomic and proteomic studies have shown an increasing molecular complexity of sporadic PD, suggesting that a broad spectrum of biochemical pathways underlie its progression. Recent investigations and the literature review suggest the potential role of deregulation of the sensitive-cysteine proteome as a convergent pathogenic mechanism that may contribute to this complexity, opening new therapeutic opportunities.