Our research covers a broad span of proteins, misfolding mechanisms, and chaperones.
We work with a number of proteins prone to misfolding:
• Prion protein (PrP)- associated with the transmissible spongiform encephalopathies (TSE)
• Amyloid-beta (Aβ) - associated with Alzheimer´s disease
• Tau-associated with Alzheimer’s disease and several Tauopathies, eg PSP and CBD
• Transthyretin - associated with familial amyloidotic polyneuropathy (Skelleftesåsjukan)
• Insulin - associated with fibril formation during biotechnological production
• Lysozyme - associated with hereditary non-neuropathic systemic amyloidosis
and the molecular chaperones:
• BiP (Hsp70)
• GroEL (Hsp60)
• GroES (Hsp10) and other HSP10 chaperones
and fluorescent proteins:
We also work with the fly Drosophila melanogaster as research model for neurodegenerative disease, typically animals expressing Aβ and Tau.
Microscope images from Drosophila melanogaster models of Alzheimers disease. The Alzheimer associated protein Aβ has been expressed in different cell types in the central nervous system of the fly and formed amyloid. The amyloid is labled with green pFTAA. Image from Jonson et al Cell Chemical Biology 2018 https://www.sciencedirect.com/science/article/pii/S2451945618301089
The basis for selective vulnerability of certain cell types for misfolded proteins in neurodegenerative diseases is largely unknown. This knowledge is crucial for understanding disease progression in the CNS. Cell specific expression of human Aβ1-42 associated with Alzheimer’s disease in Drosophila neurons resulted in concentration dependent severe neurodegenerative phenotypes, and intraneuronal ring-tangle like aggregates with immature fibril properties. Unexpectedly, expression of Aβ1-42 from a pan-glial driver produced a mild phenotype despite massive brain load of Aβ1-42 aggregates, even higher than in the strongest neuronal driver. Glial cells formed more mature fibrous aggregates, morphologically distinct from aggregates found in neurons, and was mainly extracellular. Our findings implicate that Aβ1-42 cytotoxicity is both cell and aggregate morphotype dependent.