COVID ‐19 and the impact on Alzheimer's disease pathology
Coronavirus disease 2019 (COVID-19) has rapidly escalated into a global pandemic. Many studies suggest a connection between viral infections and an increased risk of neurodegeneration, raising concerns about the neurological effects of COVID-19 and the possibility that it may contribute to Alzheimer's disease (AD) onset or worsen already existing AD pathology through inflammatory processes given that both COVID-19 and AD share pathological features and risk factors. We here review the question whether COVID-19 is a risk factor for AD and how these two conditions might influence each other. The schematic shows an overview o...
Source: Journal of Neurochemistry - October 18, 2023 Category: Neuroscience Authors: Susana Furman,
Kim Green,
Thomas E. Lane Tags: REVIEW Source Type: research
Gpr75 knockout mice display age ‐dependent cone photoreceptor cell loss
GPR75 is an orphan G protein-coupled receptor that is highly expressed in the retina. The function of the receptor in the retina is unknown. Knockout mice were characterized to determine how the absence of GPR75 affects the retina. Knockout mice exhibited an age-dependent retinal degeneration that mainly affected cone photoreceptor cells and not rod photoreceptor cells. GPR75 may play a protective role in cone photoreceptor cells. The characterized knockout mice can serve as a model to study cone photoreceptor cell loss to better understand retinal degenerative diseases that primarily affect cones. Graphic created with Bio...
Source: Journal of Neurochemistry - October 16, 2023 Category: Neuroscience Authors: Sreelakshmi Vasudevan,
Ivy S. Samuels,
Paul S. ‐H. Park Tags: ORIGINAL ARTICLE Source Type: research
Book Review: Alzheimer's Disease Research: What has guided research so far and why it is high time for a paradigm shift (Christian Behl. Springer Nature, Switzerland, 2023) 661 pp.
This is a review of a recently published book entitled ‘Alzheimer's Disease Research: What has guided research so far and why it is high time for a paradigm shift’ (book cover shown in the graphic) by Christian Behl, a leading contributor to the field of Alzheimer disease over the last three decades. It presents a personal viewpoint on the historica l developments in dementia research and therapeutics from its early beginnings through to the current day. The conflicting hypotheses, the therapeutic trials, the successes and the failures of the vast research infrastructure devoted to dissecting the aberrant pathways unde...
Source: Journal of Neurochemistry - October 14, 2023 Category: Neuroscience Authors: Anthony J. Turner Tags: REVIEW Source Type: research
Heterozygous NF1 dermal fibroblasts modulate exosomal content to promote angiogenesis in a tissue ‐engineered skin model of neurofibromatosis type‐1
This study highlights the potential of targeting exosome secretion and angiogenesis for therapeutic interventions in NF1. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - October 14, 2023 Category: Neuroscience Authors: Vincent Roy,
Alexandre Paquet,
Lydia Touzel ‐Deschênes,
Hélène T. Khuong,
Nicolas Dupré,
Francois Gros‐Louis Tags: ORIGINAL ARTICLE Source Type: research
Associations of liver dysfunction with incident dementia, cognition, and brain structure: A prospective cohort study of 431 699 adults
In this study, we investigate the longitudinal and cross-sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917;PFDR <0.001) and pe...
Source: Journal of Neurochemistry - October 13, 2023 Category: Neuroscience Authors: Pei ‐Yang Gao,
Ya‐Nan Ou,
Hui‐Fu Wang,
Zhi‐Bo Wang,
Yan Fu,
Xiao‐Yu He,
Ya‐Hui Ma,
Jian‐Feng Feng,
Wei Cheng,
Lan Tan,
Jin‐Tai Yu Tags: ORIGINAL ARTICLE Source Type: research
Trem2 deficiency attenuates microglial phagocytosis and autophagic ‐lysosomal activation in white matter hypoperfusion
In this study, we investigated the specific role of Trem2 in a mouse model of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis (BCAS). Our results showed that chronic hypoperfusion induced white matter demyelination, microglial phagocytosis, and activation of the microglial autophagic-lysosomal pathway, accompanied by an increase in Trem2 expression. After Trem2 knockout, we observed attenuation of white matter lesions and microglial response. Trem2 deficiency also suppressed microglial phagocytosis and relieved activation of the autophagic-lysosomal pathway, leading to microglial polarization to...
Source: Journal of Neurochemistry - October 13, 2023 Category: Neuroscience Authors: Xiao ‐Wei Pang,
Yun‐Hui Chu,
Luo‐Qi Zhou,
Man Chen,
Yun‐Fan You,
Yue Tang,
Sheng Yang,
Hang Zhang,
Jun Xiao,
Gang Deng,
Wei Wang,
Ke Shang,
Chuan Qin,
Dai‐Shi Tian Tags: ORIGINAL ARTICLE Source Type: research
Issue Information
Front coverTraumatic brain injury (TBI) is one of the leading causes of disability and mortality and causes significant neurological and degenerative changes. Primary injury in TBI consists of distinct neuroanatomical zones termed as contusion (Ct) and pericontusion (PC). Since their
dynamic expansion could lead to neurological deterioration, their cellular-level and molecular analysis will provide valuable information.
Proteomic and phosphoproteomic analysis in human TBI brains carried out in this study distinguished Ct, PC and away from contusion (AC). Mitochondrial dysfunction in AC could contribute to secondary injury ...
Source: Journal of Neurochemistry - October 12, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research
Voltage ‐gated calcium channels in genetic epilepsies
Voltage-gated calcium channels are abundant in the central nervous system and serve a broad spectrum of functions. Ca2+ ions act as one of the main connections in excitation –transcription, excitation–contraction and excitation–exocytosis coupling, including synaptic transmission. In recent years, many genes encoding voltage-gated calcium channel subunits have been associated with epilepsy. This review sums up the current state of knowledge on disease mechanisms a nd provides guidance on disease-specific therapies where applicable. AbstractVoltage-gated calcium channels (VGCC) are abundant in the central nervous syst...
Source: Journal of Neurochemistry - October 12, 2023 Category: Neuroscience Authors: Robert J. Lauerer,
Holger Lerche Tags: REVIEW Source Type: research
Leptin prevents aberrant targeting of tau to hippocampal synapses via PI 3 kinase driven inhibition of GSK3 β
We propose the following mechanisms by which tau can elicit synaptic dysfunction: 1. Amyloid beta (A β1-42) promotes phosphorylation and mis-localisation of tau from axons to dendrites and synapses in hippocampal neurons, resulting in receptor internalisation. Leptin prevents this via phosphoinositide 3-kinase (PI3K)-driven inhibition of glycogen synthase kinase 3 β (GSK-3β). 2. Exogenous tau applied to hippocampal slices induces receptor internalisation and blocks of long-term potentiation (LTP). The ability of leptin to prevent both aberrant processes supports the notion that leptin is a potential therapeutic target i...
Source: Journal of Neurochemistry - October 12, 2023 Category: Neuroscience Authors: Kirsty Hamilton,
Kate Morrow,
Ermione Markantoni,
Jenni Harvey Tags: ORIGINAL ARTICLE Source Type: research
Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer's disease ‐related amyloidosis
Microglia are increasingly implicated in Alzheimer's disease (AD) where they are key responders to amyloid beta plaques. While previous studies have focused on the innate immune receptors driving microglia immune responses, how microglial innate immune responses are regulated is less understood. Immunoreceptor tyrosine-based activating and inhibitory motifs (ITAM/ITIM) are commonly known to regulate innate immune responses in the periphery. Here, we review how microglia utilize ITAM- and ITIM-mediated signaling to regulate immune responses in AD amyloidosis. A better understanding of how microglial immune responses are reg...
Source: Journal of Neurochemistry - October 12, 2023 Category: Neuroscience Authors: Joshua D. Samuels,
John R. Lukens,
Richard J. Price Tags: REVIEW Source Type: research
Neuronal NADPH oxidase is required for neurite regeneration of Aplysia bag cell neurons
In this study, we investigated the role of NADPH oxidase (Nox)-derived reactive oxygen species (ROS) in neuronal regeneration following mechanical injury. We found that in vitro injury triggers higher H2O2 levels and Nox2 and Src2 activation state in regenerating growth cones of culturedAplysia bag cell neurons. Inhibition of Nox by celastrol decreased neurite regeneration rate as well as Src2 activation and F-actin content. Our data indicate that ROS derived from neuronal Nox is required for the regeneration ofAplysia bag cell neurites. AbstractNADPH oxidase (Nox), a major source of reactive oxygen species (ROS), is invol...
Source: Journal of Neurochemistry - October 11, 2023 Category: Neuroscience Authors: S. M. Sabbir Alam,
Yuichiro Watanabe,
Brooke L. Steeno,
Soumyajit Dutta,
Halie A. Szilagyi,
Alexander Wei,
Daniel M. Suter Tags: ORIGINAL ARTICLE Source Type: research
Effects of anti ‐tau immunotherapy on reactive microgliosis, cerebral endotheliopathy, and cognitive function in an experimental model of cerebral malaria
Infection of mice with Plasmodium berghei ANKA, a murine malaria species, induces remodeling of cerebral endothelial cells, a process which primes the endothelium for the recruitment of inflammatory cells and infected red blood cells to the cerebral microvasculature. Vascular pathology also leads to neuroinflammation, involving the activation of glial cells and abnormal expression of tau proteins in neurons, leading to cognitive dysfunction. Passive immunization to pathological tau with an anti-PHF-1 monoclonal antibody mitigates microglial activation and malaria-induced endotheliopathy, ultimately resulting in the preserv...
Source: Journal of Neurochemistry - October 10, 2023 Category: Neuroscience Authors: Oscar B. Akide Ndunge,
Henry J. Shikani,
Minxian Dai,
Brandi D. Freeman,
Mahalia S. Desruisseaux Tags: ORIGINAL ARTICLE Source Type: research
Neuroanatomical and cognitive biomarkers of alpha ‐synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms
We investigated synucleinopathy-associated pathogenesis of neurodegeneration using a mouse model, injecting M83 hemizygous mice with human alpha-synuclein PFF. We employed techniques such as magnetic resonance imaging (MRI) and cognitive touchscreen testing to identify markers of early alpha-synuclein toxicity in mice. We observed similar MRI-derived patterns of pathology as observed in patients with Parkinson's disease, encapsulating regions that connect to or receive input from the injections site (right dorsal striatum), along with stark cognitive impairments that precede the classical motor symptomatology. Our findings...
Source: Journal of Neurochemistry - October 8, 2023 Category: Neuroscience Authors: Stephanie Tullo,
Aline S. Miranda,
Esther del Cid ‐Pellitero,
Mei Peng Lim,
Daniel Gallino,
Anoosha Attaran,
Raihaan Patel,
Vladislav Novikov,
Megan Park,
Flavio H. Beraldo,
Wen Luo,
Irina Shlaifer,
Thomas M. Durcan,
Timothy J. Bussey,
Lis Tags: ORIGINAL ARTICLE Source Type: research
Fundamental Neurochemistry Review: Copper availability as a potential therapeutic target in progressive supranuclear palsy: Insight from other neurodegenerative diseases
Progressive supranuclear palsy (PSP) is an atypical parkinsonism for which effective treatments are lacking due to incomplete understanding of the associated biochemical events that lead to neuronal death. Herein Billings et al. speculate that compromised availability of essential copper may provide opportunity for novel therapeutic intervention. Although direct data for links between copper and key pathological features of PSP are relatively limited, it is proposed that discoveries related to Parkinson's disease (PD) and amyotrophic lateral sclerosis may provide useful insights. AbstractSince the first description of Park...
Source: Journal of Neurochemistry - October 7, 2023 Category: Neuroscience Authors: Jessica L. Billings,
James B. W. Hilton,
Jeffrey R. Liddell,
Dominic J. Hare,
Peter J. Crouch Tags: REVIEW Source Type: research
Matrix metalloproteinase ‐9: A magic drug target in neuropsychiatry?
Matrix metalloproteinase-9 (MMP-9) is an extracellularly and extrasynaptic operating protease that has been shown to play a functional role in a variety of physiological and pathological phenomena, including development, learning and memory, synaptic plasticity, and inflammation, as well as autism spectrum and mood disorders, schizophrenia, addiction and epileptogenesis. MMP-9 is markedly activated in response to various environmental insults, such as excessive maternal or early postnatal inflammation, as well as various forms of psychotrauma. Therefore, it can be proposed that MMP-9 is uniquely positioned to be considered...
Source: Journal of Neurochemistry - October 5, 2023 Category: Neuroscience Authors: Krzysztof T. Kaczmarek,
Karolina Protokowicz,
Leszek Kaczmarek Tags: REVIEW Source Type: research
