Pharmacological inhibition of asparaginyl endopeptidase by δ-secretase inhibitor 11 mitigates Alzheimer’s disease-related pathologies in a senescence-accelerated mouse model
ConclusionsPharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 31, 2021 Category: Neurology Source Type: research
Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer ’s disease and cognitively unimpaired individuals
AbstractThe development of in vivo biomarkers of Alzheimer ’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (N PS) are non-cognitive symptoms that are increasingly recognized as early manifestations of AD, the associations of NPS with AD pathophysiology in preclinical AD remain unclear. Here, we review the associations between NPS and AD biomarkers amyloid-β (Aβ), tau and neur...
Source: Translational Neurodegeneration - March 31, 2021 Category: Neurology Source Type: research
Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer ’s disease: a systematic review and meta-analysis
AbstractA lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer ’s disease (AD). Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma. Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181 (ptau181) using four ultrasensit ive methods. Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls, and that the plasma tau...
Source: Translational Neurodegeneration - March 12, 2021 Category: Neurology Source Type: research
An old weapon with a new function: PIWI-interacting RNAs in neurodegenerative diseases
AbstractPIWI-interacting RNAs (piRNAs) are small non-coding transcripts that are highly conserved across species and regulate gene expression through pre- and post-transcriptional processes. piRNAs were originally discovered in germline cells and protect against transposable element expression to promote and maintain genome stability. In the recent decade, emerging roles of piRNAs have been revealed, including the roles in sterility, tumorigenesis, metabolic homeostasis, neurodevelopment, and neurodegenerative diseases. In this review, we summarize piRNA biogenesis inC. elegans,Drosophila, and mice, and further elaborate u...
Source: Translational Neurodegeneration - March 8, 2021 Category: Neurology Source Type: research
Ecto-GPR37: a potential biomarker for Parkinson ’s disease
ConclusionGPR37 expression is increased in SN of sporadic PD patients. The ecto-GPR37 peptides are significantly increased in the CSF of PD patients, but not in AD patients. These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 26, 2021 Category: Neurology Source Type: research
Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China
AbstractParoxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmemb...
Source: Translational Neurodegeneration - February 16, 2021 Category: Neurology Source Type: research
Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer ’s disease
AbstractAs the most common form of dementia, Alzheimer ’s disease (AD) is characterized by progressive cognitive impairments and constitutes a major social burden. Currently, the invasiveness and high costs of tests have limited the early detection and intervention of the disease. As a unique window of the brain, retinal changes can reflect the pathol ogy of the brain. In this review, we summarize current understanding of retinal structures in AD, mild cognitive impairment (MCI) and preclinical AD, focusing on neurodegeneration and microvascular changes measured using optical coherence tomography (OCT) and optical cohere...
Source: Translational Neurodegeneration - February 1, 2021 Category: Neurology Source Type: research
Multitasking guardian of mitochondrial quality: Parkin function and Parkinson ’s disease
AbstractThe familial form of Parkinson ’s disease (PD) is linked to mutations in specific genes. The mutations inparkin are one of the most common causes of early-onset PD. Mitochondrial dysfunction is an emerging active player in the pathology of neurodegenerative diseases, because mitochondria are highly dynamic structures integrated with many cellular functions. Herein, we overview and discuss the role of theparkin protein product, Parkin E3 ubiquitin ligase, in the cellular processes related to mitochondrial function, and howparkin mutations can result in pathology in vitro and in vivo. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 20, 2021 Category: Neurology Source Type: research
Cross-talks among GBA mutations, glucocerebrosidase, and α-synuclein in GBA -associated Parkinson’s disease and their targeted therapeutic approaches: a comprehensive review
AbstractCurrent therapies for Parkinson ’s disease (PD) are palliative, of which the levodopa/carbidopa therapy remains the primary choice but is unable to modulate the progression of neurodegeneration. Due to the complication of such a multifactorial disorder and significant limitations of the therapy, numerous genetic approaches have been proved effective in finding out genes and mechanisms implicated in this disease. Following the observation of a higher frequency of PD in Gaucher’s disease (GD), a lysosomal storage condition, mutations of glycosylceramidase beta (GBA) encoding glucocerebrosidase (GCase) have been ...
Source: Translational Neurodegeneration - January 15, 2021 Category: Neurology Source Type: research
Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis
AbstractAccumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta...
Source: Translational Neurodegeneration - January 8, 2021 Category: Neurology Source Type: research
Cerebral spinal fluid biomarker profiles in CNS infection associated with HSV and VZV mimic patterns in Alzheimer ’s disease
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 4, 2021 Category: Neurology Source Type: research
Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer ’s disease
ConclusionsThe NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD, which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD. Further studies using different methodological approaches to identify NPS in preclinical AD are needed to validate our findings. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 4, 2021 Category: Neurology Source Type: research
Correction to: Surfen and oxalyl surfen decrease tau hyperphosphorylation and mitigate neuron deficits in vivo in a zebrafish model of tauopathy
An amendment to this paper has been published and can be accessed via the original article. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 20, 2020 Category: Neurology Source Type: research
Targeting neuroplasticity in patients with neurodegenerative diseases using brain stimulation techniques
AbstractDeficits in synaptic transmission and plasticity are thought to contribute to the pathophysiology of Alzheimer ’s disease (AD) and Parkinson’s disease (PD). Several brain stimulation techniques are currently available to assess or modulate human neuroplasticity, which could offer clinically useful interventions as well as quantitative diagnostic and prognostic biomarkers. In this review, we discuss sever al brain stimulation techniques, with a special emphasis on transcranial magnetic stimulation and deep brain stimulation (DBS), and review the results of clinical studies that applied these techniques to examin...
Source: Translational Neurodegeneration - December 7, 2020 Category: Neurology Source Type: research
Parkinson ’s disease and translational research
AbstractParkinson ’s disease (PD) is diagnosed when patients exhibit bradykinesia with tremor and/or rigidity, and when these symptoms respond to dopaminergic medications. Yet in the last years there was a greater recognition of additional aspects of the disease including non-motor symptoms and prodromal states wit h associated pathology in various regions of the nervous system. In this review we discuss current concepts of two major alterations found during the course of the disease: cytoplasmic aggregates of the protein α-synuclein and the degeneration of dopaminergic neurons. We provide an overview of new approaches ...
Source: Translational Neurodegeneration - December 1, 2020 Category: Neurology Source Type: research
