Mechanisms of Neurodegeneration: Focus on Prion Disorders, AD, and ALS

Description

An aberrant conformer, PrPSc, of the cellular prion protein, PrPC, generates the novel infectious agent (prion) that causes fatal neurodegenerative disorders such as the "mad cow disease". However, through a tight binding, PrPC can also translate into neurons the toxic message of β-rich oligomers made of PrPSc, or amyloid beta fragments implicated in AD. Using primary neuronal cultures, the research thus focuses on whether these oligomers disrupt the PrPC control that we have currently identified on Ca2+ metabolism and signaling. Dysregulation of these cell aspects are also at the basis for recognizing the molecular causes of familial ALS.

 

5 recent publications

  • LAZZARI C, PEGGION C, STELLA R, MASSIMINO ML, LIM D, BERTOLI A, SORGATO MC (2011) Cellular prion protein is implicated in the regulation of local Ca2+ movements in cerebellar granule neurons. J. Neurochem. 116, 881-890
  • STELLA R, CIFANI P, PEGGION C, HANSSON K, LAZZARI C, BENDZ M, LEVANDER F, SORGATO MC, BERTOLI A, JAMES P (2012) Relative quantification of membrane proteins in wild-type and prion protein (PrP)-knockout cerebellar granule neurons. J. Proteome Res. 11, 523-536
  • ZANETTI F, CARPI A, MENABÒ R, GIORGIO M, SCHULZ R, VALEN G, BAYSA A, MASSIMINO ML, SORGATO MC, BERTOLI A, DI LISA F (2014) The cellular prion protein counteracts cardiac oxidative stress. Cardiovasc. Res. 104, 93-102
  • MASSIMINO ML, PEGGION C, LORO F, STELLA R, MEGIGHIAN A, SCORZETO M, BLAAUW B, TONIOLO L, SORGATO MC, REGGIANI C, BERTOLI A (2015). Age-dependent neuromuscular impairment in prion protein knock-out mice. Muscle Nerve. In press, doi: 10.1002/mus.24708
  • DE MARIO A, CASTELLANI A, PEGGION C, MASSIMINO ML, LIM D, HILL AF, SORGATO MC, BERTOLI A (2015) The prion protein constitutively controls neuronal store-operated Ca2+ entry through Fyn kinase. Front. Cell. Neurosci. In press, doi: 10.3389/fncel.2015.00416

Grants

  • PRIN, “Neurodegenerative Mechanisms in Prion Disorders: Conformational Studies and Pathophysiology of the Prion Protein; Design of Possible Pharmacological Approaches”
  • Padova University sponsored Project, "Prion-based approaches to aberrant signaling in Alzheimer’s disease”
  • AriSLA “Local perturbations of Ca2+ homeostasis as possible mechanisms of fALS pathogenesis”