Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease
ConclusionIn PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - July 28, 2022 Category: Neurology Source Type: research
The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders
AbstractNeurological disorders (NDs) are characterized by progressive neuronal dysfunction leading to synaptic failure, cognitive impairment, and motor injury. Among these diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington ’s disease (HD), and amyotrophic lateral sclerosis (ALS) have raised a significant research interest. These disorders present common neuropathological signs, including neuronal dysfunction, protein accumulation, oxidative damage, and mitochondrial abnormalities. In this context, mitochondrial impa irment is characterized by a deficiency in ATP production, excessive production of r...
Source: Translational Neurodegeneration - July 4, 2022 Category: Neurology Source Type: research
Loss of tau expression attenuates neurodegeneration associated with α-synucleinopathy
ConclusionsCollectively, our data suggest that tau is likely acting downstream of αS pathology to affect neuronal homeostasis and survival. This work further supports the investigation of tau in α-synucleinopathies to identify novel disease-modifying therapeutic strategies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - July 1, 2022 Category: Neurology Source Type: research
Retraction Note: Alpha-synuclein overexpression in the olfactory bulb initiates prodromal symptoms and pathology of Parkinson ’s disease
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - June 29, 2022 Category: Neurology Source Type: research
Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases
AbstractMost neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA ’s neuroprotective action derives from animal ...
Source: Translational Neurodegeneration - June 4, 2022 Category: Neurology Source Type: research
Defective mitophagy and the etiopathogenesis of Alzheimer ’s disease
AbstractAccumulation of impaired mitochondria and energy metabolism disorders are non-negligible features of both aging and age-related neurodegeneration, including Alzheimer ’s disease (AD). A growing number of studies suggest that mitophagy disorders play an important role in AD occurrence and development. The interaction between mitophagy deficits and Aβ or Tau pathology may form a vicious cycle and cause neuronal damage and death. Elucidating the molecular mechani sm of mitophagy and its role in AD may provide insights into the etiology and mechanisms of AD. Defective mitophagy is a potential target for AD preventio...
Source: Translational Neurodegeneration - June 3, 2022 Category: Neurology Source Type: research
Impaired dynamic interaction of axonal endoplasmic reticulum and ribosomes contributes to defective stimulus –response in spinal muscular atrophy
ConclusionsThese findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - June 2, 2022 Category: Neurology Source Type: research
N-terminally truncated A β4-x proteoforms and their relevance for Alzheimer’s pathophysiology
ConclusionsThe persistence of aggregation-prone A β4-x proteoforms likely contributes to the process of amyloid formation, self-perpetuating the amyloidogenic loop and exacerbating amyloid-mediated pathogenic pathways. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - June 1, 2022 Category: Neurology Source Type: research
Correction: Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 17, 2022 Category: Neurology Source Type: research
Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer ’s disease
ConclusionsOur results suggest for the first time that melatonin alleviates tau-related pathologies through upregulation of miR-504-3p  expression by targeting the p39/CDK5 axis and provide novel insights into AD treatment strategies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 9, 2022 Category: Neurology Source Type: research
A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin
AbstractNeurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood â...
Source: Translational Neurodegeneration - May 9, 2022 Category: Neurology Source Type: research
Parvalbumin neuroplasticity compensates for somatostatin impairment, maintaining cognitive function in Alzheimer ’s disease
ConclusionsOur results demonstrate the inherent neuronal processes leading to cognitive maintenance, and describe a novel finding of endogenous cognitive resilience in an AD model. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 3, 2022 Category: Neurology Source Type: research
Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations
AbstractThe selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer ’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highligh...
Source: Translational Neurodegeneration - May 2, 2022 Category: Neurology Source Type: research
Stepping up to meet the challenge of freezing of gait in Parkinson ’s disease
AbstractThere has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson ’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi- modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field...
Source: Translational Neurodegeneration - May 1, 2022 Category: Neurology Source Type: research
Advances in the development of new biomarkers for Alzheimer ’s disease
AbstractAlzheimer's disease (AD) is a complex, heterogeneous, progressive disease and is the most common type of neurodegenerative dementia. The prevalence of AD is expected to increase as the population ages, placing an additional burden on national healthcare systems. There is a large need for new diagnostic tests that can detect AD at an early stage with high specificity at relatively low cost. The development of modern analytical diagnostic tools has made it possible to determine several biomarkers of AD with high specificity, including pathogenic proteins, markers of synaptic dysfunction, and markers of inflammation i...
Source: Translational Neurodegeneration - April 21, 2022 Category: Neurology Source Type: research
