Analysis of human brain tissue derived from DBS surgery
ConclusionsThe instruments used during routine DBS surgery are a useful source for obtaining fresh brain tissues from living patients. This approach overcomes the issues that arise from using postmortem tissues, such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain, and can be used for studying molecular aspects of DBS-treatable diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - April 13, 2022 Category: Neurology Source Type: research
α-Synuclein arginylation in the human brain
ConclusionWe propose that α-syn arginylation constitutes a potential neuroprotective mechanism that prevents its abnormal accumulation during neurodegeneration and aging in the human brain. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - April 8, 2022 Category: Neurology Source Type: research
Genetic heterogeneity on sleep disorders in Parkinson ’s disease: a systematic review and meta-analysis
AbstractA growing amount of evidence has indicated contributions of variants in causative genes of Parkinson ’s disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, includi...
Source: Translational Neurodegeneration - April 8, 2022 Category: Neurology Source Type: research
Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system
AbstractMany neurodegenerative diseases, including Alzheimer ’s disease and Parkinson’s disease, are characterised by the accumulation of misfolded protein deposits in the brain, leading to a progressive destabilisation of the neuronal network and neuronal death. Among the proteins that can abnormally accumulate are tau and α-synuclein, which can propaga te in a prion-like manner and which upon aggregation, represent the most common intracellular proteinaceous lesions associated with neurodegeneration. For years it was thought that these intracellular proteins and their accumulation had no immediate relationship with ...
Source: Translational Neurodegeneration - March 21, 2022 Category: Neurology Source Type: research
Immunotherapy for Alzheimer ’s disease: targeting β-amyloid and beyond
AbstractAlzheimer ’s disease (AD) is the most common neurodegenerative disease in the elderly worldwide. However, the complexity of AD pathogenesis leads to discrepancies in the understanding of this disease, and may be the main reason for the failure of AD drug development. Fortunately, many ongoing preclinical an d clinical studies will continually open up avenues to unravel disease mechanisms and guide strategies for AD diagnosis and drug development. For example, immunotherapeutic strategies targeting amyloid-β (Aβ) and tau proteins were once deemed almost certainly effective in clinical treatment due to the excell...
Source: Translational Neurodegeneration - March 18, 2022 Category: Neurology Source Type: research
Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis
ConclusionsAlthough the relationship between glymphatic clearance and ALS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of ALS. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 15, 2022 Category: Neurology Source Type: research
Autologous treatment for ALS with implication for broad neuroprotection
ConclusionsThis work introduces and mechanistically characterizes a new biologic for treating ALS and other complex neurodegenerative diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 11, 2022 Category: Neurology Source Type: research
Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson’s disease: a post-mortem observational study
ConclusionsPD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 8, 2022 Category: Neurology Source Type: research
Long-term hyperglycemia aggravates α-synuclein aggregation and dopaminergic neuronal loss in a Parkinson’s disease mouse model
ConclusionOur results solidify the potential link between DM and PD, providing insights into how hyperglycemia induces nigrostriatal degeneration and contributes to pathogenic mechanisms in PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 7, 2022 Category: Neurology Source Type: research
Clinical and genetic characterization of a large cohort of patients with Wilson ’s disease in China
ConclusionsOur work expanded theATP7B variant spectrum and highlighted the differences among patients with WD in age-at-onset andATP7B variants, which may provide some valuable insights into the diagnosis, counseling, and treatment of patients with WD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 28, 2022 Category: Neurology Source Type: research
RNA targets of TDP-43: Which one is more important in neurodegeneration?
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 25, 2022 Category: Neurology Source Type: research
Prodromal Parkinson's disease: hype or hope for disease-modification trials?
AbstractThe ultimate goal in Parkinson's disease (PD) research remains the identification of treatments that are capable of slowing or even halting the progression of the disease. The failure of numerous past disease-modification trials in PD has been attributed to a variety of factors related not only to choosing wrong interventions, but also to using inadequate trial designs and target populations. In patients with clinically established PD, neuronal pathology may already have advanced too far to be modified by any intervention. Based on such reasoning, individuals in yet prediagnostic or prodromal disease stages, may ...
Source: Translational Neurodegeneration - February 21, 2022 Category: Neurology Source Type: research
LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
AbstractMutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson ’s disease (PD). Mounting evidence has demonstrated pathological similarities betweenLRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a therapeutic target in PD.LRRK2 mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autop...
Source: Translational Neurodegeneration - February 14, 2022 Category: Neurology Source Type: research
Adenosine A1 receptor ligands bind to α-synuclein: implications for α-synuclein misfolding and α-synucleinopathy in Parkinson’s disease
ConclusionsThe results indicate that A1R agonists and drugs promoting a “knot” conformation of α-syn can cause α-synucleinopathy and increase neuronal degeneration, whereas A1R antagonists and drugs promoting a “loop” conformation of α-syn can be harnessed for possible neuroprotective therapies to decrease α-synucleinopathy in PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 10, 2022 Category: Neurology Source Type: research
EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid
ConclusionsOur data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 9, 2022 Category: Neurology Source Type: research
