Jun
Neuroscience Graduate School Seminar
The Neuroscience graduate school seminars are held twice a month. This is your chance to hear about the research happening in the MultiPark research environment, as well as to socialize after the presentations. Today we have presentations by:
Emma Nyberg - "THE EFFECT OF APOE GENOTYPE ON ENDOLYSOSOMAL DYNAMICS IN NEURONS"
Apolipoprotein E4 (ApoE4) is known as the most important genetic risk factor for developing Alzheimer’s disease (AD). Understanding the cellular differences between the ApoE isoforms will be crucial for understanding the fundamental pathways that are disrupted in AD and potential pathways that can be therapeutically targeted. Accumulating evidence suggests that ApoE4 alters the endosomal system of neurons, which is also one of the earliest systems affected in AD. However, our understanding of how the ApoE isoforms affect the endolysosomal pathway in neurons is still limited. We aim to understand how ApoE isoforms affectendolysosomal dynamics in neurons by studying changes in the endolysomal pathway in mature and aged neurons as well as how the pathway responds to neuronal activity.
Karin Skarping - "Huntingtin gene CAG repeats in patients with Lynch syndrome"
Huntington disease, a dominantly inherited neurodegenerative disorder, is caused by an expanded CAG repeat sequence in the huntingtin gene (HTT). Genes involved in the mismatch repair (MMR) pathway have been recognized as modifiers for age of onset, rate of progression and somatic expansion. Individuals with Lynch syndrome (LS) are prone to cancer due to heterozygous germline pathogenic variants (PV) in MMR genes, such as MLH1, MSH2, MSH6 and PMS2. In this study we consider LS-patients as a naturally occurring in vivo model to study the impact of PV in MMR genes on number of germline HTT CAG repeats and somatic expansions. Number of CAG repeats in HTT was determined using clinical standard PCR amplification and capillary electrophoresis fragment analysis in lymphocyte DNA from individuals (Lund cohort/Bochum cohort) with LS with germline PV in MLH1 (n=18/82), MSH2 (n= 19/92), MSH6 (n= 21/24), PMS2 (7/9) and matched controls (n= 19/559). We found that the number of CAG repeats in individuals with PV in MLH1 (missense PV excluded) was significantly lower compared to controls (p= 0,014). Our study shows that number of germline HTT CAG repeats is altered in individuals with MLH1-associated LS.
Emil Axell - "Solubility of the amyloidogenic core of tau"
Determining the solubility of a molecule can seem trivial and easy, just add more solute and see how much can be dissolved before it precipitates. However, due to the high metastability of proteins and the intricate mechanisms of amyloid fibril formation, the task is not necessarily easy. One way to determine the apparent solubility is to have a supersaturated solution of your amyloid peptide of interest, give the system enough time to reach equilibrium, then separate the insoluble fibrils from the soluble monomer and determine their concentration. This has been done in the lab with the Aβ40 peptide. Tau on the other hand is notoriously soluble and does not aggregate in vitro without the addition of polyanionic inducers like heparin or RNA. In this work, a smaller fragment of the full-length tau protein, spanning amino acids 304-380C322S has been used. Cryo-EM structures of ex-vivo tau tangles from Alzheimer's disease brains show that this fragment spans the amyloidogenic core of tau and this fragment has been shown to aggregate on its own in vitro without the need of inducers. Preliminary data has found the solubility of this fragment to be around 2.4 mM, determined using liquid scintillation counting, a method that would allow measurement in more complex sample matrices like cerebral spinal fluid.
About the event
Location:
I1345, BMC, I13
Contact:
diana [dot] jerman [at] med [dot] lu [dot] se