Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction
AbstractPhysical exercise is of great significance for maintaining human health. Exercise can provide varying degrees of benefits to cognitive function at all stages of life cycle. Currently, with the aging of the world ’s population and increase of life expectancy, cognitive dysfunction has gradually become a disease of high incidence, which is accompanied by neurodegenerative diseases in elderly individuals. Patients often exhibit memory loss, aphasia and weakening of orientation once diagnosed, and are unable to have a normal life. Cognitive dysfunction largely affects the physical and mental health, reduces the quali...
Source: Translational Neurodegeneration - February 27, 2023 Category: Neurology Source Type: research
Circadian disruption and sleep disorders in neurodegeneration
AbstractDisruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translationa...
Source: Translational Neurodegeneration - February 13, 2023 Category: Neurology Source Type: research
Employing nanoparticle tracking analysis of salivary neuronal exosomes for early detection of neurodegenerative diseases
AbstractNeurodegenerative diseases are a set of progressive and currently incurable diseases that are primarily caused by neuron degeneration. Neurodegenerative diseases often lead to cognitive impairment and dyskinesias. It is now well recognized that molecular events precede the onset of clinical symptoms by years. Over the past decade, intensive research attempts have been aimed at the early diagnosis of these diseases. Recently, exosomes have been shown to play a pivotal role in the occurrence and progression of many diseases including cancer and neurodegenerative diseases. Additionally, because exosomes can cross the ...
Source: Translational Neurodegeneration - February 7, 2023 Category: Neurology Source Type: research
Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer ’s disease
ConclusionsWe report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs, inducing a network performance collapse. Moreover, our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 6, 2023 Category: Neurology Source Type: research
Links between COVID-19 and Parkinson ’s disease/Alzheimer’s disease: reciprocal impacts, medical care strategies and underlying mechanisms
AbstractThe impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson ’s disease (PD) and Alzheimer’s disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could tr...
Source: Translational Neurodegeneration - January 30, 2023 Category: Neurology Source Type: research
Combined metabolic activators improve cognitive functions in Alzheimer ’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
ConclusionOur results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019,https://clinicaltrials.gov/ct2/show/NCT04044131 (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 26, 2023 Category: Neurology Source Type: research
Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson ’s disease dementia
ConclusionsTaken together, increased neurofilament immunoreactivity suggests underlying axonal injury and neurofilament accumulation in morphologically altered neurons with increased pathological burden. Importantly, we demonstrate that such neurofilament markers at least partly explain MRI measures that are associated with the neurodegenerative process. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 20, 2023 Category: Neurology Source Type: research
Correction: Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer ’s disease protects against mitochondrial dysfunction and mitigates brain pathology
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 11, 2023 Category: Neurology Source Type: research
p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer ’s disease
ConclusionsThese results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 9, 2023 Category: Neurology Source Type: research
Targeting the overexpressed mitochondrial protein VDAC1 in a mouse model of Alzheimer ’s disease protects against mitochondrial dysfunction and mitigates brain pathology
ConclusionsThe study suggests that mitochondrial dysfunction with its gatekeeper VDAC1 is a promising target for AD therapeutic intervention, and VBIT-4 is a promising drug candidate for AD treatment. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 28, 2022 Category: Neurology Source Type: research
TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a disease characterized by upper and lower motor neuron (MN) loss with a signature feature of cytoplasmic aggregates containing TDP-43, which are detected in nearly all patients. Mutations in the gene that encodes TDP-43 (TARBDP) are known to result in both familial and sporadic ALS. In ALS, disruption of neuromuscular junctions (NMJs) constitutes a critical event in disease pathogenesis, leading to denervation atrophy, motor impairments and disability. Morphological defects and impaired synaptic transmission at NMJs have been reported in several TDP-43 animal models and in vi...
Source: Translational Neurodegeneration - December 27, 2022 Category: Neurology Source Type: research
Enhanced delivery of a low dose of aducanumab via FUS in 5 ×FAD mice, an AD model
ConclusionIn conclusion, the enhanced delivery of a low dose of Adu (3 mg/kg) via FUS decreases amyloid deposits and attenuates cognitive function deficits. FUS-mediated BBB opening increases adult hippocampal neurogenesis as well as drug delivery. We present an AD treatment strategy through the synergistic effect of the combined therapy of FUS and Adu. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 27, 2022 Category: Neurology Source Type: research
Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity
AbstractAmyotrophic lateral sclerosis (ALS) is an adult-onset paralytic disease characterized by progressive degeneration of upper and lower motor neurons in the motor cortex, brainstem and spinal cord. Motor neuron degeneration is typically caused by a combination of intrinsic neuronal (cell autonomous) defects as well as extrinsic (non-cell autonomous) factors such as astrocyte-mediated toxicity. Astrocytes are highly plastic cells that react to their microenvironment to mediate relevant responses. In neurodegeneration, astrocytes often turn reactive and in turn secrete a slew of factors to exert pro-inflammatory and neu...
Source: Translational Neurodegeneration - December 26, 2022 Category: Neurology Source Type: research
ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer ’s disease with a bispecific, brain-penetrating fusion protein
ConclusionAffinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB, such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently. Furthermore, bispecific immunoPET imaging of brain A β pathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats, suggesting that this immunoPET strategy has the potential to be translated to higher species. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - December 26, 2022 Category: Neurology Source Type: research
Extracellular vesicles, from the pathogenesis to the therapy of neurodegenerative diseases
AbstractExtracellular vesicles (EVs) are small bilipid layer-enclosed vesicles that can be secreted by all tested types of brain cells. Being a key intercellular communicator, EVs have emerged as a key contributor to the pathogenesis of various neurodegenerative diseases (NDs) including Alzheimer ’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease through delivery of bioactive cargos within the central nervous system (CNS). Importantly, CNS cell-derived EVs can be purified via immunoprecipitation, and EV cargos with altered levels have been identifi ed as potential biomarkers for ...
Source: Translational Neurodegeneration - December 12, 2022 Category: Neurology Source Type: research
