CNC.IBILI

Neuro8 | Main Goals

The Group will be focused in chronic disorders that affect brain, retina, heart and kidney. Since diabetes and its complications is a main interest, diseases such as diabetic retinopathy, nephropathy, cardiomyopathy and encephalopathy will be a major focus, but also glaucoma, Parkinson’s and Alzheimer’s diseases and psychostimulants abuse.

Since many therapies for chronic disorders are not satisfactory and the development of improved therapies is needed, we will keep pursuing the following goals:
– elucidate the molecular and cellular mechanisms underlying the pathogenesis of chronic disorders affecting brain, retina, heart and kidney;
– elucidate the mechanisms of action of some drugs already used in pharmacotherapy;
– identify new potential drug targets and more efficient therapeutic options (conventional drugs, and molecular and cellular therapies) for the treatment of chronic disorders affecting those organs.

Complementary to these, we intend:
– to perform in vitro and in vivo testing for validation of new drug candidates;
– patenting new drug candidates or new therapeutic (molecular and cellular) strategies.

Additionally, particular objectives for the four sub-areas are defined inside the Group, as follows.

Vision Sciences
We have a major interest in diabetic retinopathy (DR) and glaucoma. DR is a microvascular disease and the blood-retinal barrier breakdown is a disease hallmark. Moreover, DR is characterized by neural degeneration and neuroinflammatory processes (microglia have a major role), features shared also by glaucoma. We will be looking for protective strategies against vascular and neural dysfunction/degeneration, by exploring the potential of modulating several neurotransmitter/neuromodulator systems, which include neuropeptide Y, adenosine, endocannabinoids and aldosterone. These systems can exert both neuroprotective and anti-inflammatory effects, which is an advantage.

Neuroscience and Blood-Brain Barrier
Psychostimulants like methamphetamine (METH) cause significant brain damage leading to neurological and psychiatric anomalies. Moreover, methylphenidate is the most frequently prescribed drug for the symptomatic treatment of attention deficit hyperactivity disorder. Since blood-brain barrier (BBB) damage is an early event in many neurological conditions, we intend to clarify the impact of METH and methylphenidate on BBB function, given a particular attention to neuroinflammation. We also aim to uncover if under methylphenidate use the brain becomes more susceptible to infections.
Diabetic encephalopathy is characterized by cognitive and memory impairments and hippocampus is an area mainly affected. We will explore how neuroflammation can impair axonal transport in hippocampal neurons and how this impairment can affect memory performance.

Stem Cells
The modulation of the properties of the neurogenic niche in the hippocampus or the subventricular zone is a topic of major interest. In particular, development of new experimental strategies for drug delivery (using micro and nanocarriers) and drug targets will be put in place. These tools will be applied in experimental models of demyelinating diseases and stroke/brain ischemia, to promote brain repair. Moreover, fundamental mechanisms of neurogenesis and the functional coupling between new neurons differentiation and functional integration in the hippocampal circuits with memory and learning will be investigated.

Experimental Therapeutics
Regarding chronic diseases that affect the heart, kidney and the peripheral vascular system, there is also a marked interest on inflammatory processes underlying the molecular mechanisms of disease. The Group will be focused on experimental and clinical therapeutic strategies to improve prevention/treatment of disease or ameliorate drug-induced toxicity. The main targets will be prediabetic cardiomyopathy, diabetic nephropathy, resistance to erythropoietin therapy in chronic kidney disease and atherosclerosis/dyslipidaemia.