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.

Popular description of our current research

Group:

Chao Wang
Igor Iashchishyn
Istvan Horvath

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).

Publications

Author

Title

Year sorteringsordning

Fulltext

Horvath, Istvan
Jia, Xueen
Johansson, Per; et al.

Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease.
ACS Chemical Neuroscience

2015

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Wang, Chao
Klechikov, Alexey G.
Gharibyan, Anna L.; et al.

The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade
Acta Neuropathologica, 127(4): 507-522

2014

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Kaspersen, Jørn D.
Pedersen, Jannik N.
Hansted, Jon G.; et al.

Generic structures of cytotoxic liprotides: nano-sized complexes with oleic acid cores and shells of disordered proteins
ChemBioChem (Print), 15(18): 2693-2702

2014

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Fodera, Vito
Vetri, Valeria
Wind, Thea S.; et al.

Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures
Journal of Physical Chemistry Letters, 5(18): 3254-3258

2014

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Gruden, Marina A
Davydova, Tatiana V
Narkevich, Victor B; et al.

Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates
Behavioural Brain Research, 263: 158-168

2014

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Gruden, Marina A
Davydova, Tatiana V
Narkevich, Victor B; et al.

Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms
Behavioural Brain Research, 279: 191-201

2014

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Gruden, Marina A.
Sewell, Robert D. E.
Yanamandra, Kiran; et al.

Immunoprotection against toxic biomarkers is retained during Parkinson's disease progression (vol 233, pg 221, 2011)
Journal of Neuroimmunology, 268(1-2): 99-99

2014

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Brännström, Kristoffer
Lindhagen-Persson, Malin
Gharibyan, Anna L.; et al.

A Generic Method for Design of Oligomer-Specific Antibodies
PLoS ONE, 9(3): e90857-

2014

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Clementi, Emily A.
Wilhelm, Kristina R.
Schleucher, Juergen; et al.

A Complex of Equine Lysozyme and Oleic Acid with Bactericidal Activity against Streptococcus pneumoniae
PLoS ONE, 8(11): Article Number: UNSP e80649-

2013

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Eremenko, Ekaterina
Ben-Zvi, Anat
Morozova-Roche, Ludmilla A.; et al.

Aggregation of Human S100A8 and S100A9 Amyloidogenic Proteins Perturbs Proteostasis in a Yeast Model
PLoS ONE, 8(3): e58218-

2013

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Page Editor: Ludmilla Morozova-Roche
2015-10-07

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Ludmilla Morozova-Roche

Contact Information

Umeå University
Medical Biochemistry and Biophysics
SE-901 87 Umeå, SWEDEN 

Visiting Address
KBC-building, 6th floor

Tel:  +46 90 786 5283

Fax:  +46 90 786 9795

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