Review
Neurosciences
Moxin Wu, Manqing Zhang, Xiaoping Yin, Kai Chen, Zhijian Hu, Qin Zhou, Xianming Cao, Zhiying Chen, Dan Liu
Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, with synaptic dysfunction recognized as the main cause of cognitive impairments. Pathological tau is suggested to induce synaptic dysfunction in various ways, contributing to cognitive decline in AD. Exploring the mechanism by which pathological tau impairs synaptic function is crucial for developing novel therapeutic strategies for AD.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Immunology
Zhi-Xiu Lin, Wen Yang, Qing-Qing Xu, Qiuju Yuan, Yan-Fang Xian
Summary: This study aimed to evaluate the cognitive deficits improving effects of SF on TgCRND8 mice and elucidate the underlying molecular mechanisms. The results showed that SF significantly ameliorated the cognitive deficits in TgCRND8 mice and protected primary mouse neurons against A beta 1-42 induced neurotoxicity. SF is a potent CDK5 inhibitor and a potential therapeutic agent for treatment and prevention of AD.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Claudio Gouveia Roque, Kyung Min Chung, Ethan P. McCurdy, Radhika Jagannathan, Lisa K. Randolph, Krystal Herline-Killian, Jimena Baleriola, Ulrich Hengst
Summary: In this study, it was found that beta-amyloid, a trigger of Alzheimer's disease (AD), promotes the formation of pathological CREB3L2-ATF4 transcription factor heterodimers in neurons. Through the use of AD datasets and a novel chemogenetic method, the researchers discovered that this heterodimer activates a transcription network interacting with genes differentially expressed in AD, including those associated with beta-amyloid and tau neuropathologies. The activation of CREB3L2-ATF4 also leads to tau hyperphosphorylation and secretion, as well as misregulation of the retromer, a complex linked to AD pathogenesis.
Article
Neurosciences
Charlotte S. Bold, Danny Baltissen, Susann Ludewig, Michaela K. Back, Jennifer Just, Lara Kilian, Susanne Erdinger, Marija Banicevic, Lena Rehra, Fadi Almouhanna, Martina Nigri, David P. Wolfer, Roman Spilger, Karl Rohr, Oliver Kann, Christian J. Buchholz, Jakob von Engelhardt, Martin Korte, Ulrike C. Muller
Summary: The study reveals the therapeutic potential of APPs alpha in mitigating Tau-induced synaptic deficits. Additionally, loss of interneurons leads to disrupted neuronal circuits, compromising synaptic plasticity and behavior.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Clinical Neurology
Marina Tedeschi Dauar, Anne Labonte, Cynthia Picard, Justin Miron, Pedro Rosa-Neto, Henrik Zetterberg, Kaj Blennow, Sylvia Villeneuve, Judes Poirier
Summary: This study investigates the role of the CNTN5 rs1461684 G variant and contactin 5 protein in sporadic Alzheimer's disease (sAD). The findings show that CSF contactin 5 levels increase in cognitively unimpaired individuals but decrease in mild cognitive impairment and sAD. CSF contactin 5 is correlated with sAD biomarkers and synaptic markers. The rs1461684 G variant is associated with faster disease progression in cognitively unimpaired subjects. Decreased CNTN5 mRNA levels are observed in the presence of the G allele and as a function of Alzheimer's disease stages. These results highlight the significance of the rs1461684 G variant, contactin 5 protein, and mRNA in the early stages of sAD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Xin Wang, Qian Liu, Xiao-Guang Li, Qiu-Zhi Zhou, Dong-Qin Wu, Shi-Hong Li, Yan-Chao Liu, Jian-Zhi Wang
Summary: The study showed that T217-phosphorylation exacerbates wild-type tau hyperphosphorylation with aggravated tau cleavage/fibrillization and cognitive impairments; however, overexpressing T217E on the basis P301L does not exacerbate tau phosphorylation or the P301L-induced cognitive deficits, although it aggravates tau cleavage and propagation.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Longfei Li, Yanli Jiang, Gang Wu, Yacoubou Abdoul Razak Mahaman, Dan Ke, Qun Wang, Bin Zhang, Jian-Zhi Wang, Hong-Lian Li, Rong Liu, Xiaochuan Wang
Summary: Abnormal posttranslational modifications of tau, including phosphorylation and truncation, play important roles in tau pathology and neurodegeneration. Phosphorylation of truncated tau significantly fosters endogenous tau pathology and neurodegeneration.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
M. Bell-Simons, S. Buchholz, J. Klimek, H. Zempel
Summary: This study used a laser-based axotomy model combined with confocal microscopy to investigate the distribution of Tau protein in axons and its relationship with protein transport. The results suggest that axonal damage does not lead to the accumulation of Tau protein in the cell body or an increase in AT8 Tau phosphorylation.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Longfei Li, Jin Miao, Dandan Chu, Nana Jin, Yunn Chyn Tung, Chun-Ling Dai, Wen Hu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Summary: Findings from this study suggest that the monoclonal tau antibody 77G7 effectively suppresses the seeding activity of AD O-tau and could potentially be developed as an immunotherapeutic drug to inhibit the propagation of tau pathology in AD and related tauopathies.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Santiago Rodriguez Ospina, Danielle M. Blazier, Marangelie Criado-Marrero, Lauren A. Gould, Niat T. Gebru, David Beaulieu-Abdelahad, Xinming Wang, Elizabeth Remily-Wood, Dale Chaput, Stanley Stevens, Vladimir N. Uversky, Paula C. Bickford, Chad A. Dickey, Laura J. Blair
Summary: The study found that overexpression of Hsp22 can protect synaptic plasticity and cognition in tauopathic brains, without significantly altering tau phosphorylation levels. Mass spectrometry analysis revealed that Hsp22 overexpression in neurons promotes synaptic plasticity by regulating canonical pathways and upstream regulators related to potential AD markers and synaptogenesis regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Erin E. Sundermann, Laura M. Campbell, Olivia Villers, Mark W. Bondi, Ben Gouaux, David P. Salmon, Douglas Galasko, Virawudh Soontornniyomkij, Ronald J. Ellis, David J. Moore
Summary: We examined the prevalence of AD pathological hallmarks in HIV-infected individuals and found that AD pathology was less prevalent and less severe in HIV-positive individuals compared to HIV-negative individuals. AD pathology was most consistently related to memory-related domains in HIV-positive individuals. Further studies are needed to investigate the effect of HIV status on AD pathology.
Article
Behavioral Sciences
Liangping Li, Jiawen Liang, Hongjun Fu
Summary: The study provides an update on the association between traumatic brain injury and Alzheimer's disease, focusing on Tau pathology and synaptic dysfunction. It highlights the importance of hyperphosphorylated tau aggregation and synaptic dysfunction in mediating neurodegeneration and cognitive deficits in both conditions. Additionally, the review proposes future perspectives for uncovering the complex relationship between TBI and neurodegeneration, aiming to develop potential therapeutic avenues for alleviating cognitive deficits after TBI.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Khaled S. Abd-Elrahman, Stephen S. G. Ferguson
Summary: mGluR5 is widely expressed in the brain and plays a key role in memory and learning, synaptic transmission, and plasticity. Its dysfunction, specifically in response to Aβ42 oligomers, is believed to contribute to the pathophysiology of AD. As a potential therapeutic target for AD, recent studies have demonstrated the efficacy of mGluR5 allosteric modulators in improving memory deficits and mitigating disease pathology. However, the pharmacological differences and downstream signaling activation of mGluR5 in different genders suggest the need for reevaluation of its therapeutic potential in female AD patients.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gayle Doherty, Alison Holiday, Yasaman Malekizadeh, Cosmin Manolescu, Stephen Duncan, Iona Flewitt, Kirsty Hamilton, Beth MacLeod, James A. Ainge, Jenni Harvey
Summary: Key pathological features of Alzheimer's disease (AD) include the accumulation of amyloid beta (Aβ) and metabolic dysfunction. Impairments in the leptin system have been detected in AD patients, sparking interest in targeting this system for AD treatment. This study examines the cognitive enhancing and neuroprotective actions of six-amino acid peptides derived from leptin(116-130) in promoting synaptic plasticity and improving memory tasks. The hexamers replicate the effects of leptin in promoting AMPA receptor trafficking and preventing toxic effects of Aβ on hippocampal synapses and neuronal viability. These findings further support leptin and leptin-derived peptides as potential therapeutics for AD.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Katarzyna Glombik, Jan Detka, Bartosz Bobula, Joanna Bak, Magdalena Kusek, Krzysztof Tokarski, Boguslawa Budziszewska
Summary: This study analyzed the possible link between depression and hypothyroidism, finding that WKY rats showed weakened memory processes and reduced long-term potentiation, while PTU administration in Wistar rats decreased LTP and increased basal excitatory transmission. Differences in synaptic plasticity between strains were observed, suggesting a lower sensitivity of the hippocampus to thyroid hormones in depression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)