Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
AbstractNeuroinflammation is associated with neurodegenerative diseases, such as Alzheimer ’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between t...
Source: Translational Neurodegeneration - November 26, 2020 Category: Neurology Source Type: research
Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders
ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - November 23, 2020 Category: Neurology Source Type: research
Maintaining the balance of TDP-43, mitochondria, and autophagy: a promising therapeutic strategy for neurodegenerative diseases
AbstractMitochondria are the energy center of cell operations and are involved in physiological functions and maintenance of metabolic balance and homeostasis in the body. Alterations of mitochondrial function are associated with a variety of degenerative and acute diseases. As mitochondria age in cells, they gradually become inefficient and potentially toxic. Acute injury can trigger the permeability of mitochondrial membranes, which can lead to apoptosis or necrosis. Transactive response DNA-binding protein 43 kDa (TDP-43) is a protein widely present in cells. It can bind to RNA, regulate a variety of RNA processes, and ...
Source: Translational Neurodegeneration - October 30, 2020 Category: Neurology Source Type: research
Precision medicine in Parkinson ’s disease patients with LRRK2 and GBA risk variants – Let’s get even more personal
AbstractParkinson ’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminerg ic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the...
Source: Translational Neurodegeneration - October 16, 2020 Category: Neurology Source Type: research
Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance
ConclusionsPD03 and Anle138b can selectively target oligomeric α-synuclein, resulting in attenuation of neurodegeneration in the PLP-α-syn mice. Both approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - September 23, 2020 Category: Neurology Source Type: research
SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid- β antibody in a mouse model of Alzheimer’s disease
ConclusionsThe high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging. Moreover, it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - September 20, 2020 Category: Neurology Source Type: research
Exploring the regulatory roles of circular RNAs in Alzheimer ’s disease
AbstractCircular RNAs (circRNAs) are a type of covalently closed, single-stranded circular noncoding RNA that can affect the expression of many protein-coding genes. Growing evidence has shown that circRNAs play critical roles in Alzheimer ’s disease (AD) and may have therapeutic potentials for this disease. CircRNAs play regulatory roles in neural functions and neurological disorders through diverse mechanisms, including acting as microRNA sponges or interacting with proteins to regulate selective splicing or transcription, as well as through epigenetic modification. In this review, we discuss the biogenesis and functio...
Source: Translational Neurodegeneration - September 20, 2020 Category: Neurology Source Type: research
Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer ’s disease
ConclusionsModules of tightly regulated lipids and proteins, drivers in lipid homeostasis and innate immunity, are strongly associated with AD phenotypes. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - September 20, 2020 Category: Neurology Source Type: research
The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson ’s disease
AbstractIn recent years, many studies have investigated the correlations between Parkinson ’s disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher...
Source: Translational Neurodegeneration - August 31, 2020 Category: Neurology Source Type: research
Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?
AbstractAmyotrophic lateral sclerosis (ALS) is characterized by adult-onset progressive degeneration of upper and lower motor neurons. Increasing numbers of genes are found to be associated with ALS; among those, the first identified gene,SOD1 coding a Cu/Zn-superoxide dismutase protein (SOD1), has been regarded as the gold standard in the research on a pathomechanism of ALS. Abnormal accumulation of misfolded SOD1 in affected spinal motor neurons has been established as a pathological hallmark of ALS caused by mutations inSOD1 (SOD1-ALS). Nonetheless, involvement of wild-type SOD1 remains quite controversial in the pathol...
Source: Translational Neurodegeneration - August 18, 2020 Category: Neurology Source Type: research
GCH1 variants contribute to the risk and earlier age-at-onset of Parkinson ’s disease: a two-cohort case-control study
ConclusionsThe results highlight the importance of deleterious variants and non-coding variants ofGCH1 in PD in Chinese mainland and suggest thatGCH1 mutation can influence the PD phenotype, which may help design experimental studies to elucidate the mechanisms ofGCH1 in the pathogenesis of PD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 3, 2020 Category: Neurology Source Type: research
Inflammation-induced PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons
ConclusionsThis study reported for the first time the mechanistic and biological consequences of PINCH expression in CNS neurons in diseases with a chronic neuroinflammation component. Our findings point to the maintenance of PINCH at normal physiological levels as a potential new therapeutic target for neurodegenerative diseases with impaired metabolisms. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 2, 2020 Category: Neurology Source Type: research
Increased prediction value of biomarker combinations for the conversion of mild cognitive impairment to Alzheimer ’s dementia
ConclusionA combination of two biomarkers of NDEs (A β1 –42) and SS-16 predicted the conversion of MCI to AD dementia more accurately in combination. These findings have critical implications for understanding the pathophysiology of AD dementia and for developing preventative treatments for cognitive decline. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - August 2, 2020 Category: Neurology Source Type: research
Early morning off in patients with Parkinson ’s disease: a Chinese nationwide study and a 7-question screening scale
ConclusionsWe demonstrated that EMO is a common feature for PD patients across all disease stages and put forward an EMO-specific screening card of sufficient accuracy and brevity. Meanwhile we have thrown some light upon potential determinants and negative health effects of EMO. Our findings may exert great impact on improving the awareness, recognition and management of EMO in PD patients. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - July 5, 2020 Category: Neurology Source Type: research
Nucleo –cytoplasmic transport defects and protein aggregates in neurodegeneration
AbstractIn the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates, nucleo-cytoplasmic transport defects have an emerging role. Several pieces of evidence suggest a link between neuronal protein inclusions and nuclear pore complex (NPC) damage. These processes lead to oxidative stress, inefficient transcription, and aberrant DNA/RNA maintenance. The clinical and neuropathological spectrum of NPC defects is broad, ranging from physiological aging to a suite of neurodegenerative diseases. A better understanding of the shared pathways among these condit...
Source: Translational Neurodegeneration - July 2, 2020 Category: Neurology Source Type: research
