NeuroProtectionLab
GT1 Coordinator
NeuroProtectionLab is a multidisciplinary and highly motivated research group which members belong to different areas such as pharmacology, medicinal chemistry, biotechnology, bioinformatics, biochemistry, and medicine with the common purpose of finding innovative therapies for neurodegenerative diseases (NDDs), with special interest in Alzheimer’s disease, tauopathies and cerebrovascular diseases. To do this, we develop projects that range from medical chemistry (design and synthesis of molecular models) to the testing of models in animals, including the repositioning of drugs and the fine-tuning of new in vivo neurodegeneration drugs. Our projects focus on the following lines of research:
- Pathophysiological mechanisms of NDDs: identification of targets
- Search and identification of new therapies for NDDs
Primary culture of neurons from the mouse prefrontal cortex expressing the human tau protein with the P301L mutation.
Blue: nuclei. Red: hyperphosphorylated tau at Ser202/Thr305. Green: hyperphosphorylated tau at Tyr18.
NDDs share common pathophysiological mechanisms such as aging, proteinopathy, oxidative stress, neuroinflammation, mitochondrial dysfunction, or intracellular calcium dyshomeostasis. At this point we are working at several levels:
- Aging:many of our projects are carried out in parallel in adult animals and in aged animals. This allows us to determine the impact of aging on the processes we are studying.
- Neuroinflammation-central immune response: we are interested in knowing what is the participation of the cells from the immune system in the central nervous system -the microglia- in the pathophysiology of NDDs since the immune system, with aging, becomes less competent. Likewise, we want to know what the communication signals are between "the microglia-the astrocyte-the neuron" to identify targets susceptible to pharmacological modulation that allow neurodegenerative processes to be stopped.
- Oxidative Stress: free radicals are signaling molecules necessary for proper cell function, but their excess production can be harmful. NeuroProtectionLab is interested in knowing the participation of NOXs, HO-1 or the master regulator of the antioxidant response - the transcription factor NRF2 - in neurodegenerative processes in order to find drugs that modulate these activities.
For the search and identification of new therapies for NDDs, we are working in areas such as:
- Chemical-Medical:specifically in the design, synthesis and biological evaluation of multitarget ligands (Multitarget Ligand Drugs- MTLDs), molecules that integrate two or more activities for targets involved in neurodegeneration. Specifically, we are interested in combinations of the following activities: induction of the transcription factor NRF2, inhibition of several enzymes related to neurological disorders (ACE, MAO-B, GSK-3β), modulators of nicotinic acetylcholine receptors, modulators of melatonin receptors …
- In silico screening: through these bioinformatic methodologies we seek to reposition drugs or find chemical structures that can be chemically modified with therapeutic potential in NDTs and which is based on our previous target identification studies.
Image of mouse hippocampus injected with an adeno-associated particle expressing human tau protein with the P301L mutation.
Blue: nuclei. Red: hyperphosphorylated tau at Ser202/Thr305. Green: hyperphosphorylated tau at Tyr18.
The NeuroProtectionLab group -directed by Dr. Manuela García López, Professor of Pharmacology at the Department of Pharmacology and Therapeutics- is part of:
- “Teófilo Hernando” Institute for Medicine R&D (IFTH) of the Universidad Autónoma de Madrid (UAM).
- She is principal investigator of the"Pharmacological Neuroprotection in Neurodegenerative Diseases and Stroke" Group (Group 16) at the Hospital de La Princesa Research Institute (IIS La Princesa).
- Participates in the aging hub of the European alliance CIVIS European Civic University.
