Ludmilla Morozova-Roche - Professor
Role of amyloid formation and neuroinflammation in neurodegenerative diseases, including Alzheimer’s and Parkinson’s.
In our research we focus on the role of inflammation and amyloid formation in neurodegeneration diseases including Alzheimer’s, Parkinson’s diseases and traumatic brain injury. Recent research has found a number of neurodegenerative illnesses to share links with age-dependent amyloid formations in the body. Amyloid-related diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS) and prion diseases, arise from a generic accumulation in the body of unnecessary and potentially hazardous proteinaceous amyloid products. Appearing in various organs and tissues, these aggregated deposits can eventually lead to physiological dysfunction with the degree of damage depending on many factors, including protein origin, location and individual characteristics. This means that any person can develop amyloidoses and become susceptible to age-related disease. Increasing evidence demonstrated that inflammation can play crucial role in triggering and promoting neurodegeneration. Recently we have demonstrated involvement of S100A9 protein in the amyloid-neuroinflammatory cascade in Alzheimer’s disease. Currently we conduct studies to demonstrate that neuroinflammation can be a generic mechanism involved not only in Alzheimer’s but also in other neurodegenerative diseases and can even trigger and precede the amyloid formation of well-known amyloid peptide such as Abeta in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease.
In our research we use complex approached involving a state of the art microscopic including recently purchased a Bioscope Catalyst, Bruker atomic force microscope (AFM), which is integrated into the Biochemical Imaging Center, KBC http://www.kbc.umu.se/platforms/bicu.htmltechniques, any other advanced microscopic techniques as confocal and fluorescence microscopes as well as tissue scanner. We conduct the studies at the molecular, cellular, ex vivo tissue levels and mice models. Specifically, we address the following questions:
1. Structural characterization of amyloid assemblies with particular focus on the early events in fibrillation process. Inhibition and reversal of amyloid formation. AFM and a range of biophysical and biochemical techniques are applied.
2. Revealing molecular and cellular mechanisms of amyloid toxicity, which involves identification of the toxic amyloid species and determination how they cause cell damage and death. Analysis of the apoptotic activity of proteinaceous complexes towards tumor cells.
3. Analysis of ex vivo amyloid affected tissue in order to reveal which internal factors are involved in the amyloid formation and tissue damage.
4. Evaluation of autoimmune responses to amyloids and other bookmakers in CSF and blood samples of patients with Parkinson's and Alzheimer's diseases for their early diagnostics and prognostics.
The research is multidisciplinary involving the interface of structural biology, protein sciences, cell biology, immunology and neurobiological sciences.
Post-doctoral scientists, PhD students and project students are welcome to contact us via mail or in the laboratory. All letters will be answered promptly.
Common amyloid structures proceed from a variety of native protein conformations. Proteins (A) with α-helical, α-helical / β-sheet and β-sheet structures form amyloid fibrils shown by atomic force microscopy (B). (C) Structural arrangement of amyloid fibrils derived from cryo-electron microscopy (adapted from Jimenez, J. L. et al., 1999).