RG9: Neurophysiology and Degeneration

Main goal: to integrate knowledge on the physiology and function of neuronal systems with the identification of the molecular mechanisms of neurodegeneration based on several approaches from biochemistry, cell biology, electrophysiology to behavioral assays, coupled with a diverse set of model systems (yeast, mammalian cells, flies and rodents).

Specific aims:

1. To understand the genetic and molecular mechanisms of how neurons establish and modify synaptic connectivity through ageing and under pathological conditions. There is a coordinated effort to understand how these phenomena translate into critical tasks such as motor behavior and memory formation. Such projects include uncovering the molecular and cellular mechanisms that determine which memories are kept and which are lost (R Fonseca); what cellular events determine synaptic plasticity (R Teodoro) or motor performance (C Mendes).
2. To decipher the molecular basis of age-associated pathologies such as Alzheimer's (AD) and Parkinson's (PD) diseases. In particular, to understand the precise mechanisms that contribute to the onset and progression of these diseases. These include the study of factors modulating protein misfolding and aggregation, such as the effect of disease-associated mutations and posttranslational modifications on Parkinson's disease (T Outeiro), and the identification of genetic risk factors associated with endosomal trafficking on late-onset of Alzheimer's disease (C Almeida).

Relevant collaborations: hospital services (e.g. Neurology and Rheumatology) to promote clinical projects on emerging medical predicaments of the elderly, an increasing challenge of our societies. Ultimately, this will enhance the identification of novel putative targets for therapeutic interventions.

Keywords: Neurophysiology; Alzheimer's; Parkinson's; Synaptic plasticity

Latest Publications

Rodrigues JFS, Patrício-Rodrigues CF, Sousa-Xavier VO, Augusto PM, Fernandes AC, Farinho AR, Teodoro RO (2019) Peripheral axonal ensheathment is regulated by Ral GTPase and the exocyst complex. bioRxiv 

Guimas Almeida C, Sadat Mirfakhar F, Perdigão C, Burrinha T (2018) Impact of late-onset Alzheimer's genetic risk factors on beta-amyloid endocytic production. Cellular and Molecular Life Sciences 75(14):2577-2589

König A, Vicente Miranda H, Outeiro TF (2018) Alpha-Synuclein Glycation and the Action of Anti-Diabetic Agents in Parkinson's Disease. Journal of Parkinsons Disease 8(1):33-43

Patrício-Rodrigues CF, Teodoro RO (2018) Postsynaptic RabGTPases and Exocyst: a screen at the Drosophila neuromuscular junction. Matters (in press)

Vicente Miranda H, Cássio R, Correia-Guedes L, Gomes MA, Chegão A, Miranda E, Soares T, Coelho M, Rosa MM, Ferreira JJ, Outeiro TF (2017) Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease. Scientific Reports 7, Article number: 13713