Project: Elucidation of common transcriptional targets in vulnerable DopAmine, MotorNeuron and frontotemporal Dementia disease PATHwayS

Neurodegenerative diseases (NDs) preferentially affect specific neuronal populations with corresponding distinct clinical features, even if pathogenic proteins are ubiquitously expressed. However, there is genetic and pathological evidence for activation of shared pathogenic –and perhaps compensatory– pathways across diseases. Our goal is to elucidate whether there are common pathways that can be targeted to modify disease progression, independent of specific etiopathogenesis or if they converge only at the level of lethal executers. We will start our analysis with a group of tightly connected Motor Neuron Diseases (MNDs), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) taking advantage of genetic mouse models to identify transcripts and pathways commonly affected (transversal analysis) using RNA-sequencing and computational analysis. We will include a longitudinal analysis as we anticipate that distinct transcriptional networks will be engaged at different stages. We will then investigate the expression of candidate genes in PD, FTD and ALS post-mortem brains and in human in vitro models using disease-specific induced pluripotent stem cells (iPSCs). Finally, most promising targets will be tested in vivo in MND models. We expect that our studies will unveil key shared ND pathways, operative at a stage that is still reversible, opening new avenues for the development of disease-modifying agents.

Acronym	DAMNDPATHS (Reference Number: JPND_CD_FP-688-090)
Duration	01/01/2015 - 01/01/2018
Project Topic	Neurodegenerative disease
Website	visit project website
Network	JPND
Call	A call for European research projects for cross-disease analysis of pathways related to neurodegenerative diseases

Project partner

Number	Name	Role	Country
1	Karolinska Institutet	Coordinator	Sweden
2	Fundacion Inbiomed	Partner	Spain
3	University of Milan	Partner	Italy
4	Karolinska Institutet	Partner	Sweden
5	Karolinska Institutet	Partner	Sweden