Overlaps and divergences between tauopathies and synucleinopathies: a duet of neurodegeneration
AbstractProteinopathy, defined as the abnormal accumulation of proteins that eventually leads to cell death, is one of the most significant pathological features of neurodegenerative diseases. Tauopathies, represented by Alzheimer ’s disease (AD), and synucleinopathies, represented by Parkinson’s disease (PD), show similarities in multiple aspects. AD manifests extrapyramidal symptoms while dementia is also a major sign of advanced PD. We and other researchers have sequentially shown the cross-seeding phenomenon of α-syn uclein (α-syn) and tau, reinforcing pathologies between synucleinopathies and tauopathies. The hi...
Source: Translational Neurodegeneration - March 26, 2024 Category: Neurology Source Type: research

Biases in α-synuclein immuno-quantitation: a core problem for basic and ancillary studies of Parkinson’s disease and multiple system atrophy
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 25, 2024 Category: Neurology Source Type: research

Putative novel CSF biomarkers of Alzheimer ’s disease based on the novel concept of generic protein misfolding and proteotoxicity: the PRAMA cohort
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 8, 2024 Category: Neurology Source Type: research

LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression
ConclusionsThis work supports a protective role of LRRK2 kinase inhibition in G2019S carriers and provides a rational workflow for systematic evaluation of brain-wide phenotypes in therapeutic development. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - March 4, 2024 Category: Neurology Source Type: research

Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside
AbstractThe aetiologies and origins of neurodegenerative diseases, such as Alzheimer ’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicia ns have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlig...
Source: Translational Neurodegeneration - February 27, 2024 Category: Neurology Source Type: research

α-Synuclein oligomers potentiate neuroinflammatory NF-κB activity and induce Cav3.2 calcium signaling in astrocytes
ConclusionsOur work supports a causative link between the neuron-produced α-synuclein oligomers and sustained neuroinflammation in vivo and maps the signaling pathways that are stimulated in microglia and astrocytes. It also highlights the recruitment of astrocytic Cav3.2 channels as a potential neuroprotective mediator against the α-synuclein-induced neuroinflammation.Graphical Abstract (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 21, 2024 Category: Neurology Source Type: research

Emerging role of senescent microglia in brain aging-related neurodegenerative diseases
AbstractBrain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microgl...
Source: Translational Neurodegeneration - February 20, 2024 Category: Neurology Source Type: research

Microstructural integrity of the locus coeruleus and its tracts reflect noradrenergic degeneration in Alzheimer ’s disease and Parkinson’s disease
ConclusionsIn AD and PD, the diffusion MRI-detected alterations within the LC and its tracts to the DLPFC and the M1 were associated with local noradrenergic neuronal loss within the LC, rather than noradrenergic changes in the cortex. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 9, 2024 Category: Neurology Source Type: research

Life and disease status of patients with Parkinson ’s disease during and after zero-COVID in China: an online survey
ConclusionsThe COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy  period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - February 6, 2024 Category: Neurology Source Type: research

The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing
AbstractAgeing is a crucial risk factor for Alzheimer ’s disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of agein g-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments,...
Source: Translational Neurodegeneration - January 23, 2024 Category: Neurology Source Type: research

The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases
AbstractNeurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood –brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevent ion and treatment. Preclinical investigations have unveiled multifaceted cellular effects of probucol, showca...
Source: Translational Neurodegeneration - January 22, 2024 Category: Neurology Source Type: research

Correction: A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 11, 2024 Category: Neurology Source Type: research

Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease
AbstractAlzheimer ’s disease (AD) is the most prevalent form of dementia in the elderly and represents a major clinical challenge in the ageing society. Neuropathological hallmarks of AD include neurofibrillary tangles composed of hyperphosphorylated tau, senile plaques derived from the deposition of amyloid-β (Aβ ) peptides, brain atrophy induced by neuronal loss, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is ubiquitously expressed in the central nervous system. Dysregulation of DAPK1 has been shown to contribute to various neurological diseases including AD, ischemic stroke and Par kinson’...
Source: Translational Neurodegeneration - January 9, 2024 Category: Neurology Source Type: research

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer ’s disease
ConclusionsThe findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 8, 2024 Category: Neurology Source Type: research

Nanotechnology for microglial targeting and inhibition of neuroinflammation underlying Alzheimer ’s pathology
ConclusionsThe AM –NP nanotechnology presents a multifactorial strategy to target pathological Aβ aggregation and arrest the fAβ-mediated pathological progression in microglia and neurons.Graphical Abstract (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - January 4, 2024 Category: Neurology Source Type: research