86,861 research outputs found
Synaptic localization and activity of Adam10 regulates excitatory postsynaptic compartment through N-Cadherin cleavage
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Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration
No full textMarcello Giunta,1 Eino Solje,2 Fabrizio Gardoni,3 Barbara Borroni,1 Alberto Benussi1 1Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 2Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland; 3Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, ItalyCorrespondence: Alberto BenussiClinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, Brescia 25100, ItalyTel +39 0303995632Email [email protected]: Frontotemporal dementia is a clinically, genetically and pathologically heterogeneous neurodegenerative disorder, enclosing a wide range of different pathological entities, associated with the accumulation of proteins such as tau and TPD-43. Characterized by a high hereditability, mutations in three main genes, MAPT, GRN and C9orf72, can drive the neurodegenerative process. The connection between different genes and proteinopathies through specific mechanisms has shed light on the pathophysiology of the disease, leading to the identification of potential pharmacological targets. New experimental strategies are emerging, in both preclinical and clinical settings, which focus on small molecules rather than gene therapy. In this review, we provide an insight into the aberrant mechanisms leading to FTLD-related proteinopathies and discuss recent therapies with the potential to ameliorate neurodegeneration and disease progression.Keywords: frontotemporal dementia, frontotemporal lobar degeneration, therapy, TDP-43, tau, C9orf72, GRN, MAP
Meccanismi patogenetici della malattia di Alzheimer : dalla cascata di amiloide alla sinaptopatia
No full textNew molecular mechanisms modulating NMDA receptor subunits availability at synaptic sites
No full textMAGUK proteins : new targets for pharmacological intervention in the glutamatergic synapse
No full textIn the postsynaptic density of excitatory glutamatergic synapses, membrane associated guanylate kinase (MAGUK) proteins, such as Post-Synaptic Density 95 (PSD-95), organize ionotropic glutamate receptors and their associated signalling proteins regulating the strength of synaptic activity. Modifications of MAGUK proteins function in the glutamatergic synapse such as alterations of MAGUK proteins interaction with N-Methyl-D-Aspartate (NMDA) receptors regulatory subunits are common events in several neurodegenerative disorders. Thus, a better knowledge and understanding of MAGUK structure and function as well as of the molecular events regulating MAGUK-mediated interactions in the glutamatergic synapse could lead to the identification of new targets for pharmaceutical intervention for neurodegenerative disease
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