Neuroscience aims at understanding how we perceive, move, think, and remember using billions of neurons. Every day our brain perceives massive amounts of sensory information that is processed through electrical and chemical signals in different connected networks of neurons (neuronal circuits), which must be built with high specificity in order to produce meaningful and predictable information. Neurons transmit these signals to one another at specialized sites called synapses. These are excitatory or inhibitory, and accordingly increase or decrease neuronal responses (synaptic plasticity), leading to precise patterns of learning, memory and social interactions. Several neurodegenerative and neuropsychiatric disorders have been shown to affect learning, memory and social interactions and lead to a variety of synaptic imbalances. However, the exact neuronal contribution and molecular consequences in most of these disorders remain poorly understood. Recent results using next-generation sequencing coupled to family-based studies (trios – parents and affected individual) have revealed a variety of novel risk alleles for distinct neurological disorders, therefore opening the possibility to define affected pathways in defined patient populations.
Our research focuses on novel molecular insights that are causing neurological disorders. In particular, we are approaching risk alleles by:
- Dissecting synaptic imbalances at the level of distinct neuronal subtypes.
- Addressing their role in regulating synaptic plasticity of defined neuronal circuits.
- Characterizing their impact in distinct brain regions.
CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency.
Bidinosti M, Botta P, Krüttner S, Proenca CC, Stoehr N, Bernhard M, Fruh I, Mueller M, Bonenfant D, Voshol H, Carbone W, Neal SJ, McTighe SM, Roma G, Dolmetsch RE, Porter JA, Caroni P, Bouwmeester T, Lüthi A, Galimberti I.
Science. 2016 Mar 11;351(6278):1199-203.
Molecular basis for prospective pharmacological treatment strategies in intellectual disability syndromes.
Verpelli C, Galimberti I, Gomez-Mancilla B, Sala C.
Dev Neurobiol. 2014 Feb;74(2):197-206
Atg4b-dependent autophagic flux alleviates huntington’s disease progression.
Proenca CC, Stoehr N, Bernhard M, Seger S, Roscic A, Paganetti P, Liu S, Murphy LO, Kuhn R, Bouwmeester T, Galimberti I.
PloS One. 2013 Jul; 8(7):e68357.
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