Validation and Clinical Implementation of Parkinson’s disease

Neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s disease are characterised by the irreversible loss of nerve cell function. The protein kinases c-Jun N-terminal kinase (JNK) is recognised as a player in a broad range of diseases including stroke and neurodegenerative and psychiatric diseases, while the genes LRRK2 (PARK8) and PINK1 (PARK6) are Parkinson’s associated genes that encode protein kinases. Exactly how these proteins mediate neuronal death/survival responses in the brain remains largely unknown. An investigation on LRRK2 targets is in progress. This has brought new insight regarding LRRK2 function that has broadened our understanding of Parkinson’s disease at the molecular level and provided new ground for translational research including diagnostic test development. This work is funded by the the Finnish Funding Agency for Innovation (TEKES). Read more


 

 

 

 

 

 

 

r’BIRTH : Marie Curie Initial Training Network

Molecular Regulation of Adult Neurogenesis in Anxiety and Depression

This project is part of a consortium effort to study the mechanism whereby stress kinases regulate adult neurogenesis and to develop monitoring tools to image adult neurogenesis in situ in brain. The Coffey lab studies stress kinase function in brain with a recent focus on the regulation of neurogenesis in adult brain and the accompanying processes i.e. neuronal migration, dendrite elaboration and synaptic integration. The goals of the project are to (i) develop novel monitoring tools with which to image neurogenesis in patients, this involves a proteomics study that is in close collaboration with the lab of Peter James at Lund University in Sweden, and to (ii) define the molecular mechanisms whereby stress kinases regulate anxiety and depressive responses, this utilizes transgenic mice lacking stress kinase pathway genes, to study glucocorticoid function and NMDA responses in the context of depressive disorders. Methods employed can include live confocal and multiphoton imaging, STED imaging of dendritic spines, molecular cloning, dendrite and spine architecture analysis, animal behaviour, in utero electroporation, brain phosphorylation and membrane proteomics and bioinformatics. Read more


nEUROskeleton

The hallmarks of neurons are their slender axons which represent the longest cellular processes of animals and which act as the cables that electrically wire the brain, and the brain to the body. Axons extend along reproducible paths during development and regeneration, and they have to be maintained for the lifetime of an organism. Both axon extension and maintenance essentially depend on the microtubule (MT) cytoskeleton. For this, MTs organize into parallel bundles that are established through extension at the leading axon tips within growth cones, and these bundles then form the architectural backbones, as well as the highways for axonal transport essential for supply and intracellular communication. Axon transport over these enormous distances takes days or even weeks and is a substantial logistical challenge. It is performed by kinesins and dynein/dynactin, which are molecular motors that form close functional links to the MTs they walk along. The intricate machinery which regulates MT dynamics, axonal transport and the motors is essential for nervous system development and function, and its investigation has huge potential to bring urgently required progress in understanding the causes of many developmental and degenerative brain disorders. During the last years new explanations for the highly specific properties of axonal MTs and for their close functional links to motor proteins have emerged, and it has become increasingly clear that motors play active roles also in regulating axonal MT networks. Read more