MOLECULAR NEUROBIOLOGY RESEARCH UNIT
László SIKLÓS - head of research unit, scientific adviser
Mária DELI - head of research group, scientific adviser
István KRIZBAI - head of research group, scientific adviser
The Molecular Neurobiology Research Unit is devoted to study the operation of the nervous system in physiological and pathological conditions. Understanding the details of the structure and function of the healthy brain is the prerequisite of successfully attempting to treat disease conditions ranging from a variety of degenerative diseases (Alzheimer’s- Parkinson’s disease, amyotrophic lateral sclerosis, etc.) to anxiety or depression, which affect millions of people worldwide and puts immense emotional and financial burden on their caregivers. Thus, with the final aim of development of treatment strategies, the activity of the Research Unit is focused on processes underlying either healthy adaptation or pathologic alterations of the nervous system in response to environmental challenges, including the study and manipulation of the physiological and pathological brain transport processes.
Without jeopardizing the generalization of the results, a well-defined part of the research of the group is focused on the alterations of the motor system in stress conditions, since from the aspect of explorative research its degeneration can be observed as a prototype of neurodegeneration. Indeed, even though their primary cause is mostly unknown several common mechanisms have been identified, which contribute to the loss of neurons during degeneration. These include excitotoxicity, oxidative damage, mitochondrial dysfunction, protein misfolding and aggregation, defects in axonal transport, immune-inflammatory dysfunction, impairment of the blood brain or spinal cord barrier (BBB, BSCB) and calcium mediated toxicity. According to a relatively new, but well-supported hypothesis, dysfunction of the BBB or BSCB is not only a consequence, but an active component, or even the starting point of some of these diseases. Therefore, one of the main research directions of the Molecular Neurobiology Unit is focused on understanding how the neurovascular unit functions on the molecular level in physiological and pathological conditions. Our research is aligned along two main topics. On the one hand, we aim at clarifying the role of the neurovascular unit in inflammation-associated conditions, like neurodegenerative disorders or aging. On the other hand, since the central nervous system parenchyma lacks classical lymphatic circulation, metastatic tumor cells can primarily reach the central nervous system through the blood-brain barrier. Therefore, our goal is to decipher the mechanisms of transmigration of tumor cells with the final purpose of preventing formation of brain metastases.
Since the central nervous system is uniquely protected from drug influx by the BBB or BSCB, significant amount of research capacity is devoted to develop and apply different in vitro and animal models suitable to test the delivery of putative compounds of therapeutic value in neurodegenerative disease. Thus, a research group of the Research Unit focuses on two areas: (i) improving drug delivery across biological barriers by opening tight intercellular junctions and targeted drug delivery across the blood-brain barrier by nanoparticles; (ii) finding protective molecules and mechanisms acting at the blood-brain barrier to potentially prevent or treat pathologies related to diabetes, Alzheimer's disease and epilepsy. As research tools culture models of biological barriers including the blood-brain, blood-cerebrospinal fluid, nasal, pulmonary and intestinal barriers are used. Recently a new integrated microfluidic and microelectronic device has been developed to improve the study of barriers in cooperation with the Biomolecular Electronics research group.