Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson ’s disease
AbstractParkinson ’s disease (PD) is the most common neurodegenerative movement disorder, which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain areas. The detailed pathogenic mechanisms underlying the selec tive loss of dopaminergic neurons in PD are unclear, and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in PD. However, the formation of α-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD, possib...
Source: Translational Neurodegeneration - February 4, 2019 Category: Neurology Source Type: research
Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer ’s disease
ConclusionsMore studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 1, 2019 Category: Neurology Source Type: research
Suppression of astrocytic autophagy by αB-crystallin contributes to α-synuclein inclusion formation
ConclusionsThis study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 18, 2019 Category: Neurology Source Type: research
Better survival in female SOD1 -mutant patients with ALS: a study of SOD1 -related natural history
ConclusionsThe results highlight a distinct mutational distribution and natural history spectrum in ALS patients carryingSOD1 mutations in China. A prominent mild disease progression was observed in female patients, which had rarely been reported in the previous literature. This finding, together with the detailed analysis of natural history among each mutation, can have important implications for future genetic counselling andSOD1-targeted clinical trials. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 8, 2019 Category: Neurology Source Type: research
Transcranial direct current stimulation enhances theory of mind in Parkinson ’s disease patients with mild cognitive impairment: a randomized, double-blind, sham-controlled study
ConclusionsWe show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI, and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 7, 2019 Category: Neurology Source Type: research
Amyloid, tau, pathogen infection and antimicrobial protection in Alzheimer ’s disease –conformist, nonconformist, and realistic prospects for AD pathogenesis
ConclusionAD is a multi-factor complex disorder, which likely requires a combinatorial therapeutic approach to successfully slow or reduce symptomatic memory decline. A better understanding of how various causal and/or risk factors affecting disease onset and progression will enhance the likelihood of conceiving effective treatment paradigms, which may involve personalized treatment strategies for individual patients at varying stages of disease progression. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 24, 2018 Category: Neurology Source Type: research
Correction to: Alterations of brain local functional connectivity in amnestic mild cognitive impairment
In the original publication of this article [1] surname of the first author is wrong. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 24, 2018 Category: Neurology Source Type: research
Dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and motor neuron loss in the spinal cord of ALS mouse model
ConclusionsOur data revealed the dynamic changes of CX3CL1/CX3CR1 axis and an imbalanced M1/M2 microglial activation during ALS pathological progression. These findings may help identify potential molecular targets for ALS therapy. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 21, 2018 Category: Neurology Source Type: research
Efficacy and safety of rasagiline in Chinese patients with early Parkinson ’s disease: a randomized, double-blind, parallel, placebo-controlled, fixed-dose study
ConclusionsRasagiline is effective, safe, and well tolerated as monotherapy for the treatment of Chinese PD patients.Trial registrationClinicaltrials.gov:NCT01556165. Registered 13 Mar 2012. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 6, 2018 Category: Neurology Source Type: research
Rare TBK1 variants in patients with frontotemporal dementia and amyotrophic lateral sclerosis in a Chinese cohort
ConclusionsThis study enlarges the genetic and phenotypic spectrum ofTBK1 mutation in a Chinese cohort. Our data indicates thatTBK1 mutation is not a common cause for ALS and FTD in Chinese patients. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 4, 2018 Category: Neurology Source Type: research
GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis
ConclusionsOur findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron survival. Gene expression responses were consistent with neurotrophic effects, ECM modulation, and activation of the Notch and hedgehog neurodevelopmental pathways. This multifaceted mechanism of action is unique among existing ALS drug candidates and may be applicable to multiple neurodegenerative diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 3, 2018 Category: Neurology Source Type: research
Alterations of brain local functional connectivity in amnestic mild cognitive impairment
ConclusionsThis study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN, executive control network, visual network, and sensorimotor network. These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks. These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI. Confounding factors merit much attention and warrant future investigations. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 7, 2018 Category: Neurology Source Type: research
Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome
DiscussionThese findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 6, 2018 Category: Neurology Source Type: research
Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons
ConclusionsOur studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs. Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 5, 2018 Category: Neurology Source Type: research
Aberrant functional connectivity network in subjective memory complaint individuals relates to pathological biomarkers
ConclusionWe found impaired local, but not global, intrinsic connectivity networks in SMC individuals. Given the relationships between DC value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - October 19, 2018 Category: Neurology Source Type: research
