Syncell Inc’s Post

Have you ever wondered how neuronal cells look? In our sector, Rūta Sniečkutė investigates various mammalian cells, with her primary aim being to discern the impact of different amyloids upon them. Below you can observe a glimpse into her ongoing research: neuroblastoma cells (SH-SY5Y) labelled with different fluorescent markers and after 2 days of incubation with Amyloid beta peptide (depicted in green, forming fibrils), one of the key proteins associated with Alzheimer's disease. #alzheimersdisease #Fluorescence #Cells #VilniusUniversity

Our latest paper in collaboration with Martin Ulmschneider is now available to read in ACS Omega. In this manuscript, Zhiwen Zhong has combined coarse-grain and all-atom molecular dynamics simulations to identify the key pairs of residues in the transmembrane domains of the TREM2 and DAP12 proteins that interact in order to stabilise the complex that the two proteins form. As mutants of TREM2 have been found to be risk factors for Alzheimer's Disease, we are hoping that these findings may be useful in identifying novel strategies to fight this (and potentially other) neurodegenerative disease(s). 👀 https://lnkd.in/emPYfB4M

Can bigger biceps protect you from Alzheimer's? Last week a study was published that gives us more insight into the connection between muscle and Alzheimer's (and stroke). Researchers were able to show a causal relationship between muscle mass (measured as appendicular lean mass) and risk of stroke and Alzheimer’s Disease (AD). Genetically predicted, high lean muscle mass was causally associated with a decrease risk of AD and stroke. Said another way, low lean muscle mass was associated with an increase in stroke and AD. What’s more, the study adjusted for BMI, LDL-C, and atrial fibrillation - all factors that are associated with stroke and/or AD risk. Meaning muscle alone seemed to be a contributor. Take away: This study adds to the mounting evidence that we should be prioritizing a healthy amount of muscle and preventing muscle loss at all costs. So if you haven’t yet this week, this is your chance to hit the weight room. See the comments for the study ________________________________ Find this insightful? Check out the newsletter https://lnkd.in/eUSAWTCe

Neurons malfunctioning in Parkinson's disease (PD) are often riddled with clumps of a protein called α-synuclein. But how exactly does this protein aggregation disrupt cellular health? The recently published research in Molecular Brain (co-authored by Shilpi Chaurasia from Excelra) sheds light on this critical aspect of PD progression. Discover: ➡️The Link Between α-synuclein and Cellular Chaos: Delve into how α-synuclein aggregation disrupts vital processes within neurons. ➡️A Deep Dive into Cellular Proteomics: Analyze protein changes in a PD mouse model using advanced techniques, revealing major shifts linked to α-synuclein. ➡️Unveiling the Body's Protein Management System: Explore how the body responds to α-synuclein misfolding, potentially identifying new therapeutic targets. ➡️Hope for New Treatments: Understanding α-synuclein's impact on cellular protein management opens doors for novel PD therapies! Download the full publication for a deeper dive into this exciting research: https://lnkd.in/gzQpXiwz #ParkinsonsDisease #Excelra #Proteostasis #Neuroscience #Research #Proteomics Shilpi Chaurasia, PhD Chandra Sekhar Pedamallu Uzma Saeed Puneet Saxena Amar Thyagarajan, PhD Maarten Braspenning Jan Ghyssaert

Parkinson's disease (PD) affects over 10 million people worldwide and costs nearly $25 billion annually in the United States alone. This progressive disorder, caused by the degeneration of dopamine-producing cells in the brain, has both genetic and environmental contributors, with recent studies even implicating the gut microbiome. The Michael J. Fox Foundation for Parkinson's Research and Taconic Biosciences are committed to advancing research to develop better therapies. Today, we are excited to introduce the Floxed Parkin mouse, a new model to accelerate Parkinson’s research and improve patient outcomes. Learn more: https://bit.ly/4bOeIBZ

To maintain network stability in the face of altered synaptic activity, neurons engage a feedback mechanism termed homeostatic scaling; however, this process is thought to be disrupted during Alzheimer's disease progression. Check out our recent work where we hypothesize that the dynamic changes in proSAAS expression play a critical role in hippocampal proteostatic processes, both in the context of normal homeostatic plasticity and in the control of protein aggregation during Alzheimer's disease progression. https://lnkd.in/e5DhwGty

Mathematical Computation Model for Alzheimer's Disease (AD) The following changes are identified as key drivers of AD. ASGR: a transmembrane protein that mediates endocytosis and lysosomal degradation of glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues. HSP90AA1: a heat shock protein that functions in aiding proper folding of specific target proteins by use of an ATPase activity. KCNH2: a votage-activated potassium channel found in cardiac muscle cells, nerve cells, and microglia.  Expected are increased expression of CDK5, DLG4, Bax, and P53. Dysregulated/increased calcium ions inside cells/neurons. Abberant phosphorylation of tau protein.  Ineffective clearance of plaques, damaged neurons and synapses, and infectious agents.

New connection between impaired autophagy and heart failure Autophagy is a natural, self-serving mechanism in which the body removes damaged or dysfunctional parts of a cell and recycles their components toward cellular repair or energy production. Scientists weren't sure what mechanisms underlie mitochondrial and cardiac dysfunction in the setting of impaired autophagy. Using a mouse model with autophagy dysfunction in heart cells, the research team found that autophagy regulates the enzyme NNMT, whose levels were increased in this heart failure model. Inhibiting the activity of this enzyme with a small molecule led to an improvement in heart failure even though autophagy failure persisted. The study elucidated a chain event that explains how and why impaired autophagy can lead to cardiac dysfunction. The first step of this chain is the accumulation of a protein known as SQSTM1. Increased SQSTM1 activates a signaling protein called NF-κB (also known as RELA). NF-κB enters the nucleus and causes increased activity of the gene that encodes the enzyme known as nicotinamide N-methyltransferase (NNMT). NNMT ultimately leads to a breakdown of NAD+ precursors, ultimately lowering NAD+ levels. Low NAD+ levels then cause mitochondrial and cardiac dysfunction. #ScienceMission #sciencenewshighlights https://lnkd.in/gBB5YX3i

I am happy to share that our paper has just been published in Science Advances, entitled "Human Brain Glycoform Co-regulation Network and Glycan Modification Alterations in Alzheimer’s Disease"

Researchers leveraged artificial intelligence to explore the connection between the gut microbiome and Alzheimer's disease. They utilized AI to assess how metabolites from gut bacteria interact with cell receptors, potentially influencing Alzheimer's progression. The research highlights significant metabolite-receptor pairs, including the beneficial interaction between agmatine and the CA3R receptor, which may protect against Alzheimer’s-related brain damage. These groundbreaking findings not only advance the understanding of Alzheimer's but also point towards new therapeutic strategies for diseases linked to gut microbiome activity. Learn more: https://lnkd.in/gviKafNH One love #brain #gut #metabolites #alzheimer