Julie K. Andersen, Ph.D.
Professor
Buck Institute for Research on Aging
Development of Mitophagy-inducing Small Molecules as Therapeutics for Aging and Alzheimer’s Disease
Alzheimer’s disease (AD) is the leading cause of dementia in those over the age of 65. An underlying process believed to contribute to subsequent neuropathology is loss in mitochondrial function, normally maintained by clearance of defective mitochondria via mitophagy. The small molecule urolithin A (UA) has been demonstrated by several labs, including our own, to be neuroprotective in a variety of mouse AD models. As part of an independent small molecule screen carried out by the lab, we identified a second structurally-related compound we named ‘mitophagy inducing compound’ or MIC. Using C. elegans as an initial validation tool, we showed that both compounds significantly improve mitochondrial function, protect against neuronal cell loss in disease models, and extend lifespan of wildtype animals. These protective effects were found to be translatable to both in vitro and in vivo mammalian models. Recent studies have led to identification of potential drug targets which may serve as novel therapeutic avenues for the disorder. These studies may have important implications for understanding signaling events elicited by these compounds driving their disease-modulating effects.
Mohamed Farah, Ph.D.
Associate Professor in Neurology & Neuroscience
Johns Hopkins University School of Medicine
Degeneration and Regeneration of hiPSC-Derived Peripheral Axons
Axonal dysfunction and degeneration are major early pathological features of neurodegenerative diseases. The focal deformations of axons to form spheroids and swellings, generally referred to as “beads on a string”, are the precursors to axonal fragmentation and degeneration. We investigate early axonal degeneration of human induced pluripotent stem cell (iPSC)-derived motor neurons. Toward this, we have developed a three-dimensional (3D) platform where axonal pathologies can be reliably and reproducibly investigated over time, and have identified a set of differentially expressed axonal mRNAs as intervention targets.
In a second line of research, we are studying peripheral axon regeneration. Peripheral axons have substantial plasticity to regenerate after injury in rodent models. However, human axonal regrowth is very slow, and in most cases, does not result in sufficient functional recovery in disorders of peripheral nerves. While investigating axonal regeneration of iPSC-derived motor neurons, we identified a mutant line that exhibits accelerated rate of axonal regeneration compared to isogenic control. To interrogate molecules responsible for this accelerated rate of outgrowth, we profiled and analyzed RNA expression of axons and cell bodies from mutant and control lines, and identified differentially-expressed genes as prime candidates that we are currently investigating.
Anna Hudson, Ph.D.
Senior Research Fellow
College of Medicine and Public Health
Flinders University
Neural Control of the Human Respiratory Muscles
Jose Parraca, Ph.D.
Professor
Department of Sport and Health
University of Evora
Symptoms and Brain Aging in Fibromyalgia
Fibromyalgia (FM) is a chronic condition characterized by widespread pain, fatigue, sleep disturbances, and cognitive dysfunction, commonly referred to as “fibro fog.” Emerging evidence suggests that FM may be associated with accelerated brain aging, potentially due to neuroinflammatory processes, alterations in neurotransmitter systems, and structural and functional brain changes. Neuroimaging studies indicate a reduction in gray matter volume, altered connectivity in pain-processing networks, and impaired neuroplasticity, which may contribute to symptom severity. Additionally, chronic pain and associated stress in FM could exacerbate age-related cognitive decline and neurodegeneration. Understanding the intersection between FM symptoms and brain aging is crucial for developing targeted interventions to mitigate cognitive impairment and improve the quality of life in affected individuals. This review explores the neurobiological mechanisms linking FM to brain aging and discusses potential therapeutic strategies, including neuromodulation, cognitive training, and non-pharmacological approaches.
Camila Vorkapic, Ph.D.
Associate Professor
Department of Medicine
Universidade Tiradentes
Neuroscience and Mental Health: Protocols for Well-being
The search for well-being is a constant in human life and neuroscience has opened new ways to achieve this condition. During the talk Neuroscience and mental health: protocols for well-being, I will provide a revolutionary view on how we can improve life quality and well being through easy and science-based protocols.
Introduction/Background: The human brain is complex, but it is far from perfect: we cannot regulate our emotions well, we prefer instant gratification, we suffer from relationships, we feel depression and anxiety and we prefer drugs to changing behavior. Are we condemned to not feeling well throughout our lives? Can our brains really change? Viewing the brain as a machine blinds us to the physical realities of mental functions and how we can improve them. We ignore that the brain is a product of evolution, the chemical nature of everything we do, how happiness is a habit and how simple practices can change our mental state. This talk is not just about what the brain is, but mainly about how this self-knowledge can improve our quality of life. In addition to fascinating descriptions of how the brain works, in this talk, you will learn scientifically proven strategies for reshaping your brain and behavior, and experiencing greater well-being.
Monika Wiech , Ph.D.
Assistant Professor
Gdansk University of Physical Education and Sport
Changes in Mood State After Single Health-Related Training Session Depending on the Space and Environment in the Elderly
Poster Presentations
Matthew Brander, Max Mortimer, Katya Ilyuchenko-Hodges, Nathaneil Allen, Gunes Uzer Ph.D., Brad Morrison Ph.D., Cheryl Jorcyk Ph.D., Greg Hampikian Ph.D., Masihhur Laskar
Nilufar Ali, Ph.D.*
*Principle Investigator, Assistant Research Professor, Biomolecular Research Center
Bella Grant, Spencer Pettigrew, Katelin Crutcher, Alicia Johnson, Jet Taylor
Mariane Bacelar, Ph.D.*
*Principle Investigator, Assistant Professor, Kinesiology
Mental Health in Older Adults: Investigating the relationship between depression symptoms and physical activity at the brain level
Depression is one of the leading causes of disability world-wide. In older adults, it can lead to worse outcomes, including higher mortality rates. Physical activity has been proposed as a cost-effective alternative to treat depression symptoms. However, it’s still unknown whether these benefits can be seen at the brain level. Thus, in this study, we measured older adults (N=30)’ brain activity using electroencephalography (EEG) and extracted the EEG-measure Reward Positivity (RewP), an index of reward sensitivity that is inversely correlated with depression symptoms. We also collected participants’ self-reported levels of engagement in physical activity via the Yale Physical Activity Survey and depression scores via the Geriatric Depression Scale. We predicted that participants experiencing more depression symptoms would show a smaller RewP amplitude, but that this relationship would be weaker for participants that are more physically active. Results showed a negative relationship between depression scores and RewP amplitude, but this association was not statistically significant (p = .141). The possible moderating effect of physical activity was also not statistically significant (p = .533). In sum, at least in the present study, physical activity levels did not seem to influence reward sensitivity in older adults showing varied levels of depression symptoms.
Carson Konop
AP Research Class, Bishop Kelly High School
Neurodevelopmental Comorbidities in Early Onset 5q-SMA Treated with Disease-Modifying Therapies: A Scoping Review
Recent studies have reported possible neurodevelopmental comorbidities in some early onset 5q-spinal muscular atrophy (5q-SMA) patients treated with disease-modifying therapies (DMT). This scoping review aims to determine the current state of the published and grey literature on neurodevelopmental comorbidities in early onset 5q-SMA patients treated with nusinersen, risdiplam, or onasemnogene abeparvovec. Eligible records included primary literature (journal papers excluding review articles), and conference proceedings (abstracts or posters) published in 2016 or later. A total of 6,310 database and grey literature records were screened, of which five primary literature and six conference proceedings were included. Ten records used quantitative approaches (the other mixed methods) while specific outcome measures varied. Mixed findings were reported on association of worse cognitive or developmental outcomes with gender, lower SMN2 copy number, and motor function. Authors most often explained findings by citing unknown brain injury or pathophysiology, use of non-disease specific tests, effect of motor or communicative function on exposure to environmental stimulation, and lack of SMN protein in non-spinal cord neurons. This review underscores the need for research into the longitudinal neurodevelopmental profile of these patients, creation of disease-specific outcome measures, and exploration of the neuropathophysiological characteristics of early onset 5q-SMA patients treated with DMTs.
Jiahao Pan
Biomedical Engineering Doctoral Program, Boise State University
Shuqi Zhang, Ph.D.
Department of Kinesiology, Boise State University
Aging-induced increase in top-down coupling from DLPFC to SMA/M1 and decrease in inter-limb motor coordination during standing tasks
Deficits in inhibitory control have been considered a major reason for age-related decline in postural stability. Given this, older adults commonly present increased reliance on the prefrontal cortex (PFC) to compensate for the deficits of inhibitory control; however, its impact on different motor cortices remains unclear. Hence, this study aimed to investigate the aging effects on the inhibitory control from PFC to motor cortices and inter-limb coordination during dual-task standing. Thirteen young and fourteen older adults were recruited in this study. Participants performed single-task and dual-task standing. Ground reaction force, enter of pressure, muscle activity, and cortical activation were measured. The older group showed greater functional coupling from intra- hemispheric dorsolateral PFC (DLPFC) to supplementary motor area (SMA) (right, p = 0.009 & left, p = 0.003) and left DLPFC to right M1 (p = 0.020) than the young group across task conditions. Also, the older group had greater inter-tibialis anterior coherence at 15-35 Hz (p = 0.001) and inter-soleus coherence at 35-55 Hz (p = 0.003) during dual-task than single-task standing. Furthermore, the older group showed greater variability of inter-foot coordination in the medial-lateral direction than the young group during dual-task standing (p = 0.031). Our results indicate that older adults present stronger top-down functional coupling from DLPFC to SMA/M1 compared to young adults in both single-task and dual-task standing, highlighting excitatory control deficit with aging. This failure to inhibit the DLPFC on SMA/M1 in older adults may lead to impaired motor coordination between lower limbs during dual-task standing.
Jonathon Reeck
Assistant Research Professor, Biomolecular Research Center
Abu Sayeed Chowdhury, Luke Woodbury, Shin Pu, Julie Oxford
Harnessing Monoclonal Antibodies to Target Tumor-Associated Collagen in Brain Tumors
Glioblastoma (GBM) is the most prevalent and aggressive primary malignant brain tumor, accounting for 14.2% of all brain tumors and a staggering 50.1% of all malignant brain tumors. The prognosis for patients with GBM remains exceptionally poor, with a dismal five-year survival rate of only 6.9% and a median survival of just eight months. Beyond mortality, brain tumors, particularly GBM, significantly impair patients’ quality of life, leading to a range of physical, emotional, and cognitive challenges, including persistent fatigue, cognitive dysfunction, personality changes, motor deficits, and seizures. A unique characteristic of glioblastoma lies in the altered expression and organization of collagen within the tumor microenvironment. In contrast to the normal adult brain, which contains very low levels of collagen, glioblastoma exhibits an upregulation of collagen gene expression. Monoclonal antibodies, with their inherent ability to specifically recognize and bind to unique protein sequences, can be designed to target the protein sequences encoded by cancer cells. This targeted approach holds the potential to selectively disrupt the role of the abnormally expressed collagen in GBM that is highly specific to tumor cells while minimizing damage to healthy brain tissue. Here, we demonstrate that the cancerous cells express Collagen type XI alpha-1 (COL11A1), presenting a direct therapeutic target. We generated antibodies to target distinct domains of COL11A1 and verified that the antibodies target the protein in human cell lines. Next, the unique antibody sequences were determined by de novo peptide sequencing using mass spectrometry. Using this information, we deployed a computational modeling approach to determine the antibody structure and characterize the antibody-antigen interactions to further guide development of immunotherapies. These antibodies are promising candidates for CAR-T cell therapy, monoclonal antibody treatments, or antibody-drug conjugates targeting COL11A1 on glioblastoma cells. This direct targeting of COL11A1 on glioblastoma cells offers a novel immunotherapeutic strategy for this aggressive brain tumor.