Supra Fibrillar Amyloid Assemblies on the cytoskeleton

 

Parkinson`s disease (PD) is a neurodegenerative disease and until today no treatment is found to cure patients suffering from it. The hallmark of PD is the degeneration & loss of neurons in the substantia nigra in the brain. This is accompanied and maybe caused by the formation of protein clumps or fibrils inside these cells. These clumps are named Lewy Bodies and Lewy neurites and mainly consist of a protein called α- synuclein. In Parkinson's Disease, this naturally monomeric protein aggregates to from fibrils that form mentioned protein clumps above. The actual effect of these inclusions on tissue & neurons, how and why they develop is yet not clear.

The cytoskeleton is a cellular "skeleton" contained within the cytoplasm. It consists of monomeric proteins that polymerize into fibrils and filaments fulfil their biological function. It is described in literature (Sousa et al., 2009) that the monomeric form of α- Synuclein interacts with actin, one of the cytoskeletal proteins, yet the role and strength of the interaction is not understood.

The formation of α- Synuclein fibrils in PD might disturb in the functioning of the naturally occurring filament structures of the cytoskeleton. Taking into account that the cytoskeleton plays an important role not only in cellular transport mechanisms but also in cell movement and stability, cell functions might be significantly affected by α- synuclein fibrils. To elucidate this, the interaction of these fibrillar structures has to be studied.

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SHSY-5Y Cells with labeld cytoskeleton & α- synuclein. Colocalisation of α- Synuclein with the cytoskeleton.

PhD student: Christian Raiss
Project leader: Mireille Claessens