Our projects are focused on the following lines of research:
Primary culture of mouse prefrontal cortex neurons expressing human tau protein with the P301L mutation.
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 and 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 of the immune system of the central nervous system -the microglia- in the pathophysiology of NDDs, given that the immune system, with aging, becomes less competent. Likewise, we want to know which are the communication signals between “the microglia-the astrocyte-the neuron” in order to identify targets susceptible to pharmacological modulation to stop neurodegenerative processes.
Oxidative stress: free radicals are signaling molecules necessary for proper cellular functioning, but an excess in their production can be detrimental. 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 search for drugs that modulate these activities.
Image of mouse hippocampus injected with an adenoassociated particle expressing human tau protein with the P301L mutation.
Blue: nuclei. Red: tau hyperphosphorylated at Ser202/Thr305. Green: tau hyperphosphorylated at Tyr18.
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 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: NRF2 transcription factor induction, inhibition of several enzymes related to neurological disorders (ACE, MAO-B, GSK-3β), nicotinic acetylcholine receptor modulators, melatonin receptor modulators...
In silico screening: through these bioinformatics methodologies we seek to reposition drugs or find chemical structures amenable to chemical modification with therapeutic potential in NDs and which is supported by our previous target identification studies.
The NeuroProtection Lab - led by Dr. Manuela G. López, Professor of Pharmacology of the Department of Pharmacology - is part of:
Fundación “Teófilo Hernando” de I+D del Medicamento (FTH) of the Universidad Autónoma de Madrid (UAM).
She is principal investigator of the Group “Pharmacological neuroprotection in neurodegenerative diseases and stroke” at the Research Institute of the Hospital de La Princesa (IIS La Princesa).
She participates in the aging hub of the European alliance CIVIS European Civic University.
Email manuela.garcia@uam.es for more information about projects and the lab.