9^th Global Neuroscience Conference November 21-22, 2016 Melbourne, Australia

Biography:

Ana Maria Enciu is assistant professor in Cell Biology at Carol Davila University of Medicine and  research assistant at Victor Babes Institute of Pathology. She has completed her PhD in neurosciences with a study on blood-brain barrier tight junction proteins.  She continued with a postdoctoral training in neurooncology. She has published more than 20 papers  and has been serving as an editorial board member for Austin Alzheimer’s and Parkinson’s Disease Journal since 2014. 

Abstract:

Background: Amyloid precursor protein (APP) is a membrane protein highly expressed in the brain, involved in the pathogeny of Alzheimer`s disease. Recently, protein dimers were reported to occur in vitro, with impact on pathologic metabolization and senile plaque formation.

Aim: Our study investigated whether the expression of APP is dependent on a membrane scaffolding protein – caveolin and if in native state APP can be found in dimeric or oligomeric complexes.

Material and method: brain cortex was prelevated from 7-9 mo old normal and caveolin knockout mice and investigated for amyloid precursor protein by reducing and non-reducing electrophoresis, followed by western blotting. Membranes were next separated by ultracentrifugation and investigated for APP containing macromolecular complexes by non-denaturating, blue native electrophoresis

Results APP expression was modified by the absence of caveolin, depending on the brain region. Electrophoretic separation of macromolecular complexes from mouse brain cortex was dependant on the extraction buffer and type of gel. No dimeric or low-rank oligomers were highlited with the selected protocols.

Conclusion: APP dimers were not present in the investigated brain regions even under mild protein extraction conditions. We propose that dimerization is either an in vitro occurrence, or is masked by association with another membrane proteins in macromolecular complexes.

Acknowledgment: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation CNCS-UEFISCDI, project number PN-II-RU-TE-2014-4-1534.

 

Biography:

Weidong Le, M.D., Ph.D., is a neurologist/scientist with a major research interest in neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease and ALS. He graduated from Shanghai 2^nd Medical University with a doctoral degree in 1988, and received postdoctoral training at Dr. Stanley Appel’s laboratory from 1989-1991. He was promoted to Professor of Neurology in 2005 at Baylor College of Medicine, and since 2013 he has been appointed as the Director of Center for Translational Research on Neurological Diseases, and Vice President of 1^st Affiliated Hospital, Dalian Medical University. He is a full affiliate member of Houston Methodist Research Institute. He has published over 200 SCI papers in peer review journals and 7 scientific books, and serves as board member or associate editor for 8 international journals.

Abstract:

Amyotrophic lateral sclerosis (ALS) is an adult-onset devastating neurodegenerative disease resulted from the selective death of motor neurons (MNs) associated with abnormal protein aggregation in the spinal cord and brain. We have demonstrated that autophagy impairment may underlie the pathogenesis of ALS. Mutations in the genes encoding SOD1, TDP-43, OPTN and VCP can cause misfolding proteins and autophagy induction. It is still under debate whether autophagy has a protective or detrimental role in ALS. We have found that the macroautophagy is specifically activated in the MNs of SOD-1 mouse model of ALS at early stages. In addition, we have demonstrated that mTOR-dependent autophagy enhancer rapamycin treatment in the ALS animal model causes accumulation of AVs, but fails to reduce the level of mutant SOD1 aggregates, suggesting the abnormal autophagic flux in ALS. In addition, rapamycin treatment results in severe mitochondrial impairment, higher Bax levels and greater caspase-3 activation. On the contrast, application of mTOR independent autophagic enhancer trehalose prolongs the motor neuron survival and ameliorates autophagic flux defect in the ALS model. Recently a study of whole exome sequencing in 2,874 ALS patients vs 6,405 controls, identified TANK-Binding Kinase 1 (TBK1) as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome). These observations reveal a key role of the autophagic pathway in ALS, which may provide useful information designing to target on autophagy for the potential therapeutic intervention of this devastating disease.

Biography:

Dr. Malykhina is Associate Professor at the University of Colorado Denver.  She directs a Neurourology laboratory focused on neurophysiology of the lower urinary tract and functional chronic pelvic pain disorders, with particular emphasis on the mechanisms underlying the processing of sensory nociceptive information, neurogenic bladder dysfunction in neurodegenerative disorders, and mechanosensitivity of the overactive bladder. Dr. Malykhina is a Center Director for the Colorado P20 Center on Interdisciplinary Research in Benign Urology supported by the NIH grant (P20-DK097819). She is an active member of many international societies, and serves on the review panels for the NIH and DoD study sections.

Abstract:

Multiple sclerosis (MS) is an auto-inflammatory disease of the CNS that affects approximately 400,000 people in the United States alone and more than 2.1 million people worldwide. Lower urinary tract symptoms (LUTS) are present in 70–80% of MS patients, causing great discomfort and having a negative effect on the quality of the individual’s social, occupational and sexual life. Neurogenic LUTS include urinary urgency, urinary incontinence, nocturia, urinary hesitancy, overflow incontinence, a sensation of incomplete emptying, urinary retention, and a weak urinary stream. The most common symptom reported by MS patients in remission is urgency of micturition followed by urinary frequency. In approximately 10–15% of patients, bladder symptoms are present at the onset of MS when there may be few lesions identified in the spinal cord and/or brain. In patients with established MS, bladder symptoms are prevalent and often associated with symptoms of bowel and sexual dysfunction. Identification and development of urinary tract protective therapies in neurological diseases has proven to be a major challenge, because of an already substantial LUT compromise at the time of presentation to a urologist. Therapeutic approaches for neurogenic LUTS primarily include anti-muscarinic drugs as well as intermittent self-catheterization to facilitate complete bladder emptying. Given the unfavorable side effect profile of these medications and poor persistence on therapy, as well as the burden of catheterization on a debilitated population, more innovative therapeutics are desperately needed.  In the quest for therapeutics, a greater understanding of the pathophysiology and patterns of disease is also required.  

Biography:

  

Abstract:

CONCLUSIONS AND RELEVANCE Criminal behavior is more common in patients with bvFTD and semantic variant of primary progressive aphasia than in those with AD and is more likely to be an early manifestation of the disorder. Judicial evaluations of criminality in the demented individual might require different criteria than the classic “insanity defense” used in the American legal system; these individuals should be treated differently by the law. The appearance of new-onset criminal behavior in an adult should elicit a search for frontal and anterior temporal brain disease and for dementing disorders.

Biography:

Edoardo Sinibaldi (MSc Aerospace Engineering, 2002, University of Pisa; Ph.D. Mathematics for Technology and Industry, 2006, Scuola Normale Superiore, Pisa; Post-Doc at The Biorobotics Institute, Scuola Superiore Sant’Anna, Pontedera), is with the Italian Institute of Technology since 2009, formerly as Senior Post-Doc, then as Researcher. His current research interests include biorobotics, in particular medical robotics, and modeling for biomedical applications. He serves as reviewer for nearly twenty journals. He has published one book, three book chapters, more than forty peer-reviewed papers, and two patents (by also demonstrating the first flexible probe able to physically build its track while being deployed).

Abstract:

Central Nervous System pathologies are one of the world's leading causes of disability. Despite the availability of advanced interventional techniques, many surgical tasks are still very challenging because of complex anatomical constraints. Moreover, in many cases therapy control in hampered by the lack of a thorough, quantitative understating of the related underlying physical phenomena. Both aspects motivate the development of novel approaches, including the introduction of robotic platforms and tools, and modeling frameworks.

On the robotics side, we will illustrate a platform that encompasses, in particular, a lightweight robot fostering synergistic robot–surgeon integration. We demonstrated its potential for mitigating some risk factors in neurosurgery by addressing a model ventriculostomy, in collaboration with neurosurgeons. At the tool level, we will illustrate a novel design approach that permits to achieve flexible scopes to be deployed over a given trajectory (the whole shaft, not only the tip), thus avoiding undesired/harmful contacts.

On the modeling side, we will address the numerical investigation of intrathecal drug delivery (ITDD) in the cervical subarachnoid space. The growing interest in ITDD is mainly motivated by its potential for bypassing the shielding effect of the blood-brain barrier to macromolecules. However, ITDD is affected by several parameters, many of which are little understood. We will show some recent results (obtained in collaboration with the University of Oslo and the University of Idaho) regarding the effects of catheter placement on ITDD, also encompassing drug transport to the cord.