Article 1944Brain Science**
December 21, 2023day
Science Times
nature communications：New research shows how important a protein is in maintaining the homeostasis of cell membranes
*: Alzheimer's disease.
Recently, researchers at Aarhus University in Denmark studied the structure, function, and mechanism of action of the ATP8B1 protein, which flips lipid molecules in cell membranes that play a key role in bile biosynthesis. In addition, recent studies have found a strong association between genetic variants within the ATP8B1 gene regulatory region and resilience in Alzheimer's disease.
Using state-of-the-art cryo-electron microscopy techniques, the research team captured nine different states associated with lipid transport and determined the structure of these states at a resolution of 24-3.1 å。These structural insights, combined with functional and computational studies, reveal the inner workings of the human ATP8B1-CDC50A flipping enzyme complex and how it is finely regulated by a specific regulatory lipid known as phosphatidylinositol (PIP).
JAMA Neurol: Neuronal EVS - Synuclein as a Biomarker for Parkinson's Disease
*: Home of exosomes.
Parkinson's disease (PD) is the most common movement disorder and is characterized by a long prodromal phase that begins years before the clinical manifestations of classic motor symptoms. A recent study used a large number of samples across cohorts to establish assay sensitivity and specificity, and investigated the relationship between this blood-based test and dopaminergic neurodegeneration, pathology, and phenotypic transformation.
In all cohorts, L1EV-synuclein will distinguish participants with a probability of having more than 80 percent of preparkinson's disease from current and historical healthy control populations, regardless of initial diagnosis. L1EV-synuclein was elevated in high-risk participants with a positive CSF seed amplification assay and exceeded the established threshold in 80 cases where PD or related dementia developed. The findings suggest that L1EV-synuclein should be combined with a prodromal marker to stratify those at high risk of developing PD and associated Lewy-body disease.
Molecular cell: Double-shot proteins have been linked to Parkinson's disease and breast cancer**
*: Biocom.
A recent study described how the protein ubiquitin is modified during bacterial infection. The study details the steps to make lysine 6 polyubiquitin proteins, in which a long chain of ubiquitin molecules is linked together by the amino acid lysine. This form of ubiquitin may be associated with the development of Parkinson's disease and breast cancer.
The article states that HECT-type ubiquitin ligases (including BHECT and EHECT) are able to affect the fate of proteins in different ways, depending on the form of monomer or polymeric ubiquitin signal to which they are attached. This paper reveals the entire ubiquitin ligation process by resolving the key details of the three BHECT structures in the ready, ubiquitin-loading state. One of the structures provides a rare perspective on the ligation of polyubiquitin chains, thus providing a method to relink the BHECT and EHECT ubiquitin ligase polyubiquitin specificity. The study of this evolutionarily unique BHECT family has revealed the basic principles of the action of key bacterial phenons and HECT-type ubiquitin ligases.
SCI ADV: AI Screening Targeted AMPA to Inhibit Small Molecule** Multiple Sclerosis
*：bioartmed
Conventional theories suggest that multiple sclerosis (MS) is an autoimmune disease in which an inflammatory response produced by activated T cells triggers demyelination and white matter lesions in the nervous system. Recently, Professor Fang Liu's research group from the University of Toronto has broken through the traditional theoretical viewpoint and developed a small molecule compound that plays a role by targeting a new mechanism that regulates AMPA receptor-mediated excitotoxicity.
The solution proposed by the study goes beyond immunomodulatory drugs and creatively proposes a new ** strategy--- which focuses on protecting neurons and myelin sheath and does not produce *** Although the existing immunomodulatory drugs in clinical practice are very effective in controlling the autoimmune response of MS, these drugs are almost helpless against neurodegeneration and nerve damage. Strategies and candidate compounds can well compensate for this shortcoming, and have broad application prospects and clinical development value.
iBrain Review: Wnt Signaling in Synaptogenesis in Alzheimer's Disease
*: Wiley.
Typical symptoms of AD, such as memory loss, learning difficulties, and difficulty expressing emotions, are caused by sudden triggering problems. Therefore, further insight into the molecular mechanisms that promote and maintain these synapses is needed. The WNT signaling pathway has been implicated in many serious diseases, including AD. Studies have shown that the absence or dysregulation of WNT signaling triggers the pathogenesis of AD.
Recently, Wang Wenyuan, the Interdisciplinary Research Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, and Huashan Hospital Affiliated to Fudan University, made a review of the relationship between WNT signaling and AD. Considering the regulatory role of WNT signaling in synaptogenesis, this will contribute to a better understanding of synaptogenesis, AD pathology, and new research pathways involved in WNT.
Age ageing: The role of the cerebral lymphatic system in aging-related cognitive decline
*: New frontiers in Metz Neuro.
The discovery of the cerebral lymphoid system provides a new perspective for studying brain protein homeostasis and provides a promising target for the prevention or ** of neurodegenerative diseases. Recently, researchers from the Department of Neurology of the Second Affiliated Hospital of Zhejiang University conducted a retrospective study on cognitive dysfunction, retinopathy and cerebrovascular lesions (CIRCLE) in the elderly, and found that cerebral lymphatic function plays a protective role in the cognitive decline associated with normal aging, which can be used as a potential target for the prevention of cognitive decline in the future.
BMJ Sub-Journal: Peer support is essential for medication** for people with severe mental illness
*: Biological exploration.
Most psychiatric disorders can be treated with antipsychotic medications and mood stabilizers, but they can be very serious, especially in the early stages, which can lead to very low adherence to medications. A recent study sought to understand how shared decision-making between patients and clinicians could improve the situation. Researchers have found that a person-centred approach, coupled with a trusting relationship between patients and clinicians, can support patients with serious mental illness in making medication-related decisions and ensure they receive the right medication at the right time and at the right dose. In addition, professional, effective peer support can help fill gaps in medication advice. Empathy and shared experiences make patients more receptive to the advice of their peers than they do with professionals who have no relevant experience, and help them feel more in making decisions.
The Lancet:A prospective association study of socioeconomic status, healthy lifestyles, and early-onset and late-onset dementia
*: The Lancet
Recently, a new study published by a team of professors from Huazhong University of Science and Technology pointed out that there are large differences in risk factors for early-onset and late-onset dementia, among which lower socioeconomic status is significantly associated with an increased risk of early-onset dementia, and this association is more significant in patients with type 2 diabetes. In addition, unhealthy lifestyles only partially mediated the impact of socioeconomic status on dementia. The findings suggest that in addition to promoting healthy lifestyles, other measures are needed to improve the social determinants of health in order to prevent the occurrence of dementia.
Reviewer: Simon