Gilberto Fisone

Education
1990 – Ph.D. Stockholm University.
1991-1994 – Postdoctoral Fellow, The Rockefeller University, New York.
1994-1995 – Assistant Professor, The Rockefeller University, New York.
1996-2000 – Assistant Professor, Department of Neuroscience, Karolinska Institutet.
2000-2006 – Associate Professor, Department of Neuroscience, Karolinska Institutet.
From 2006 – Professor of Neuroscience, Department of Neuroscience, Karolinska Institutet.

Current Commissions of trust

2022-present: Member of Academia Europaea.

2022-present: Secretary, International Basal Ganglia Society (IBAGS).

2020-present: Board of the Swedish Basal Ganglia Society (SWEBAGS).

2018-present: Scientific Advisory Board, Neuroscience Inst. Cavaliere Ottolenghi, Turin, Italy.

2018-present: Scientific Committee, Dargut and Milena Kemali Foundation

2018-present: Chair, Department of Neuroscience, Karolinska Institutet. 

2014-present: International Union of Basic and Clinical Pharmacology (IUPHAR) Subcommittee on Dopamine Receptors

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder after Alzheimer's disease and is diagnosed based on the appearance of tremor, rigidity, and bradykinesia, secondary to the loss of midbrain dopamine neurons projecting to the basal ganglia. In addition to the cardinal motor symptoms, PD is accompanied by a wide range of comorbidities, which include olfactory and sleep disturbances, affective disorders and cognitive impairment. These conditions are often refractory to and may even be exacerbated by standard dopamine replacement therapies against PD. Treatment of PD with L-DOPA or dopamine receptor agonists effectively reduces motor deficits, but is often accompanied by the development of motor complications, or dyskinesia, and obsessive-compulsive disorders, including pathological gambling and addictive-like behaviour. Our work is based on the characterization of animal models reproducing these various disorders, combined with multiscale analyses to identify molecular, cellular and circuit abnormalities as potential targets for therapeutic interventions.

Non-motor symptoms in Parkinson’s disease

A major research line centres on the non-motor comorbidities commonly observed in PD patients, which often appear during the prodromal phase of the disease. We have set up a toxin-based mouse model of early-stage PD, which reproduces several of these conditions. We are using a toxin-based mouse model of early-stage PD to investigate signaling and circuit abnormalities linked to anxiety and depression. Other projects focus on circadian rhythm and sleep disorders, which are commonly observed in both de novo and medicated PD patients. Our mouse model of PD is characterized by disrupted rest/activity and endogenous circadian rhythm. In a similar model, we identified important changes in sleep architecture and micro-structure, indicative of excessive daytime sleepiness and sleep fragmentation, which are frequently observed in PD patients. These studies provide a behavioral framework for the identification of mechanisms involved in PD-related sleep disorders and of potential therapeutic interventions.

Molecular mechanisms of L-DOPA-induced dyskinesia

We have identified several signal transduction components of the cAMP, ERK and mTOR cascades causally linked to the dystonic and choreic uncontrollable movements (dyskinesia) developed in response to administration of L-DOPA. Based on this conceptual background, we provided evidence in support of the involvement of impaired autophagy in L-DOPA-induced dyskinesia. The results of this study indicate that autophagy promoting drugs, including those approved for the treatment of cancer and metabolic disorders, may also be introduced in the clinic as anti-dyskinetic agents.

Obsessive compulsive disorders in Parkinson’s disease