Neuroscience
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The p75 neurotrophin receptor (p75NTR) is a multifunctional protein that regulates cellular responses to pathological conditions in specific regions of the nervous system. Activation of p75NTR in certain neuronal populations induces proteolytic processing of the receptor, thereby generating p75NTR fragments that facilitate downstream signaling. Expression of p75NTR has been reported in neurons of the ventral midbrain, but p75NTR signaling mechanisms in such cells are poorly understood. ⋯ Furthermore, inhibition of c-Jun N-terminal Kinase (JNK) decreased p75NTR cleavage induced by oxidative damage. Altogether, these results support a mechanism of p75NTR activation in which oxidative stress stimulates JNK signaling, thereby facilitating p75NTR processing via a ligand-independent mechanism involving induction of metalloprotease and γ-secretase activity. These findings reveal a novel role for JNK in ligand-independent p75NTR signaling, and, considering the susceptibility of mesencephalic neurons to oxidative damage associated with Parkinson's disease (PD), merit further investigation into the effects of p75NTR on PD-related neurodegeneration.
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It has been demonstrated Inhibitor Kappa B Kinase β (IKKβ) facilitates autophagy, which in turn mediates p-Tau protein clearance. However, the specific regulatory mechanism in Alzheimer's disease (AD) remains unclear. Firstly, AD model was generated by the intracerebroventricular (ICV) injection of the Β-amyloid 1-42 (Aβ1-42) peptide. ⋯ Findings indicated that Aβ1-42 inhibited autophagy and up-regulated p-Tau protein expression; Overexpression of IKKβ and DJ-1 all rescued the autophagy inhibited by Aβ1-42 and down-regulated p-Tau protein expression induced by Aβ1-42; DJ-1 up-regulated IKKβ via p-VHL, further promoted autophagy and reduced the expression of p-Tau protein; DJ-1 knockdown inhibited autophagy and up-regulated p-Tau protein expression, resulting in delayed behavior in mice. In conclusion, IKKβ, modulated by DJ-1/p-VHL, reduces p-Tau accumulation via autophagy in AD's disease model. This study may provide theoretical basis for the treatment of AD.
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This study aimed to investigate the alterations in brain networks in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) based on a population-specific brain template. Previous studies on AD brain networks using graph theory rarely adopted brain templates specific for certain ethnicities. In this study, patients were divided into 3 groups: AD (n = 24), MCI (n = 27), and healthy controls (HCs, n = 33), and all of the subjects are Chinese. ⋯ Several graph metrics were significantly correlated with cognitive function and the ability to engage in daily activities. The findings suggest that altered graph metrics in the frontal gyrus may reflect brain plasticity, and that patients with MCI may have unique graph metric alterations in the cerebellum. Future graph analysis studies on functional brain networks in AD and MCI based on population-specific brain atlases for particular ethnicities may prove valuable.
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The schizophrenia-susceptibility gene, dystrobrevin-binding protein 1 (DTNBP1), encodes the dysbindin protein and mediates neurotransmission and neurodevelopment in normal subjects. Functional studies show that DTNBP1 loss may cause deficient presynaptic vesicle transmission, which is related to multiple psychiatric disorders. However, the functional mechanism of dysbindin-mediated synaptic vesicle transmission has not been investigated systematically. ⋯ Moreover, dysbindin loss accompanied slightly decreases in Munc18-1 and snapin expression levels, which are associated with vesicle priming and synaptic homeostasis under high-frequency stimulation. Together, we inferred that dysbindin directly interacts with Munc18-1 and snapin to mediate calcium dependent RRP replenishment. Dysbindin loss may lead to RRP replenishment dysregulation during high-frequency stimulation, potentially causing cognitive impairment in schizophrenia.
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Functional connectivity in EEG resting-state is not stable but fluctuates considerably. The aim of this study was to investigate how efficient information flows through a network, i.e. how resting-state EEG networks are organized and whether this organization it also subject to fluctuations. Differences of the network organization (small-worldness), degree of clustered connectivity, and path length as an indicator of how information is integrated into the network across time was compared between theta, alpha and beta bands. ⋯ It is therefore the interplay of local processing efficiency and global information processing efficiency in the brain that fluctuates in a frequency-specific way. Properties of how information can be integrated is subject to fluctuations in a frequency-specific way in the resting-state. The possible relevance of these resting-state EEG properties is discussed including its clinical relevance.