The Krogan Lab researchers are currently performing mechanistic follow-up studies on a subset of the protein-protein interactions they  identified. “Our affinity purification mass spectrometry studies on sacsin have revealed a protein-proteininteraction with DAPK...

One of the hallmark features of ARSACS is dysfunction and eventual death of Purkinje cells in the cerebellum, which contributes to ataxia. Strikingly, not all Purkinje cells become ill and die: rather, specific patterns of vulnerability and resilience to cell death...

It is well established in neurodegenerative diseases that early therapeutic intervention - ideally before neurodegenerative cascades begin to breakdown neuronal function - is key to the success of disease-modifying therapies. Yet we do not understand the early...

ARSACS is characterised by the lack of sacsin expression, and the formation of intermediate filaments bundles in neurons and fibroblasts derived from skin biopsies. Our strategy over the last years has been aimed at developing a replacement therapy, by peptide and/or...

Glial cells play key roles in developmental and neurodegenerative disorders, including some with remarkable similarities with ARSACS, such as Alexander disease and Giant Axonal Neuropathy. We and others have found high levels of sacsin expression in rodent and human...

The viability of neurons in the brain depends on a complex series of interconnected biochemical reactions that constitute cellular metabolism. Disruption of these metabolic pathways is associated with neurological conditions, including Alzheimer’s and Parkinson’s....

Despite extensive research, the underlying causes of neurodegeneration in ARSACS still remain unclear, and thus there is a need for identifying effective therapies for ARSACS patients. My lab over the past several years has focused on characterizing the changes of...

We identified in murine Purkinje cells a specific interaction of sacsin with proteins regulating transmembrane ion balance, which are required for tuning the firing properties of these neurons. Our functional studies support a deregulation of ion conductance in...

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a juvenile progressive movement disorder caused by mutations in a gene called SACS, which produces a protein with the same name (SACS or sacsin). The disease is characterized by very early onset,...

Retinal and eye abnormalities are among the clinical hallmarks in ARSACS and have been described since first reports. Those defects have been confined to an unexplored field by a molecular point of view, compared to those related to brain and cerebellum that have been...

ARSACS is incurable neurodegenerative disorder and there is an urgent need to define new therapies. The expected results of this project are to evaluate, through preclinical studies, the effectiveness and usefulness of an experimental diet containing neuroprotective...