Metabolic and Bioenergetic Drivers of Neurodegenerative Disease: Neurodegenerative Disease Research and Commonalities with Metabolic Diseases

Grazyna Söderbom, PhD is founder of Klipspringer AB. She received her BSc 1st Class Hons in Pharmacology & Toxicology from King’s College, London and PhD in Neuroscience from the University of London. She spent one year of her undergraduate studies investigating the role of the AT2-receptor subtype at Ciba-Geigy under the tutelage of Dr Marc de Gasparo. As a Wellcome Trust PhD Scholar in Prof. Peter Jenner’s Neurodegenerative Research Group, Grazyna focused on the aetiology of Parkinson’s disease, specifically the relevance of antioxidant enzymes in the basal ganglia and Parkinson’s pathogenesis. After working as a Post-Doctoral Research Fellow at the Clinical Age Research Unit at King’s College Hospital, Grazyna joined Zeneca/AstraZeneca Pharmaceuticals, which included five years as Global Brand Manager in Cardiovascular Medicine in Sweden. She was involved in the global marketing and communications behind the antihypertensive Atacand® and the launch of Atacand Plus®. Having discovered a strong interest in strategic medical communications, Grazyna launched Klipspringer in 2013, which specializes in scientific, medical and strategic writing and consultation for Academia, Bio-Pharma and beyond. Grazyna is passionate about “all things science”, especially neuroscience, and the effective sharing of scientific knowledge to all levels of audiences. She has published scientific research of her own and now supports others in their scientific and medical communications. Grazyna is particularly interested in the potential implications of the link between metabolic disease and neurodegenerative disorders. Russell Esterline, PhD is currently a VP Global Medicines Leader at AstraZeneca Pharmaceuticals leading the advancement of late stage metabolic products towards registration and approval and beyond. He received his B.S. in Chemistry from Juniata College and his PhD in Toxicology from Rutgers University/UMDNJ Joint Graduate Program in Toxicology. He completed his Post-Doctoral training at the Johns Hopkins School of Hygiene and Public Health. Both pre- and post-graduate research focused on the impact of toxicants on mitochondrial function. At AstraZeneca, Russell led the development of CRESTOR (rosuvastatin) through its LCM delivery stage (METEOR, CORONA, AURORA, JUPITER, SATURN clinical trials) and more recently led the development of FARXIGA (dapagliflozin) through global approval and launch. As the FARXIGA lead, Russell became interested in understanding the underlying mechanism(s) behind the unique SGLT2i-driven benefit in patients with type 2 diabetes and has published a novel theory describing the metabolic underpinning of this benefit. If correct, this theory may have implications beyond the proven benefits on the heart and kidney into the CNS, a possibility which is currently being pursued through collaborations with leading scientists in the field. Jan Oscarsson is MD, PhD in Physiology and Registered physician trained in internal medicine. He was appointed Professor in Physiology, especially Endocrinology and Integrative metabolism, in 2003 and was recruited by AstraZeneca R&D the same year. His academic work has focused on metabolic regulation in cell culture, animal and clinical studies. He has also been interested in the hormonal regulation of neurogenesis in collaboration with the late Professor Peter Eriksson. At AstraZeneca R&D, he has had several different positions in R&D, including Head of Section of Molecular Metabolism and Disease Area Portfolio Leader focusing on diabetes and metabolic regulation. Since 2013, he is Director Physician in Clinical Development, working on type 2 diabetes, dyslipidemia and fatty liver disease. During the last few years he has conducted studies to determine the mechanisms behind the unique SGLT2i-driven benefits in patients with type 2 diabetes, and together with Russ Esterline PhD, published a novel theory describing the metabolic underpinning of this benefit. Dr. Mattson is a Professor of Neuroscience at Johns Hopkins University School of Medicine. After receiving his PhD degree from the University of Iowa, Dr. Mattson completed a postdoctoral fellowship in Developmental Neuroscience at Colorado State University. He then joined the Sanders-Brown Center on Aging at the University of Kentucky College of Medicine where he advanced to Full Professor. From 2000-2019 Dr. Mattson was the Chief of the Laboratory of Neurosciences at the National Institute on Aging in Baltimore where he brought neuroscience research to the forefront at that NIH Institute. Dr. Mattson’s research is aimed at understanding molecular and cellular mechanisms of brain aging and the pathogenesis of neurodegenerative disorders. His work has elucidated how the brain responds adaptively to challenges such as fasting and exercise, and he has used that information to develop novel interventions to promote optimal brain function throughout life. Dr. Mattson is among the most highly cited neuroscientists in the world with over 150,000 citations and an ‘h’ index of over 200. He was elected a Fellow of the American Association for the Advancement of Science, and has received many awards including the Metropolitan Life Foundation Medical Research Award, the Alzheimer’s Association Zenith Award and the Santiago Grisolia Chair Prize. He was the founding Editor and Editor-in-Chief of Ageing Research Reviews and Neuromolecular Medicine, and is currently a Reviewing or Associate Editor for the Journal of Neuroscience and Trends in Neurosciences.

1. Status and future directions of clinical trials in Alzheimer’s disease
Germán Plascencia-Villa and George Perry
2. Tracking the potential involvement of metabolic disease in Alzheimer's disease—Biomarkers and beyond
Jose A. Luchsinger and Henrik Zetterberg
3. Brain glucose and ketone utilization in brain aging and neurodegenerative diseases
Dimitrios Kapogiannis and Konstantinos I. Avgerinos
4. Disturbances in brain energy metabolism in insulin resistance and diabetes and Alzheimer's disease—Learnings from brain imaging biomarkers
Kerstin Heurling, Edvin Johansson and Antoine Leuzy
5. APOE and metabolic dysfunction in Alzheimer’s disease
Lance A. Johnson
6. Status and future directions of clinical trials in Parkinson's disease
Grazyna Söderbom
7. Involvement of GABAergic interneuron dysfunction and neuronal network hyperexcitability in Alzheimer's disease: Amelioration by metabolic switching
Mark P. Mattson
8. The mitochondrial hypothesis: Dysfunction, bioenergetic defects, and the metabolic link to Alzheimer's disease
Russell H. Swerdlow
9. MAM and C99, key players in the pathogenesis of Alzheimer’s disease
Marta Pera, Jorge Montesinos, Delfina Larrea, Rishi R. Agrawal, Kevin R. Velasco, Irina G. Stavrovskaya, Taekyung D. Yun and Estela Area-Gomez
10. Experimental studies of mitochondrial and lysosomal function in in vitro and in vivo models relevant to Parkinson’s disease genetic risk
Ria Thomas, Penelope J. Hallett and Ole Isacson
11. Endosomal-lysosomal dysfunction in metabolic disorders and Alzheimer's disease
Michael F. Almeida, Ben A. Bahr and Stephen T. Kinsey
12. Neuroinflammation, microglial activation, and glucose metabolism in neurodegenerative diseases
Paul Edison
13. The NLRP3 inflammasome as a bridge between neuro-inflammation in metabolic and neurodegenerative diseases
Grazyna Söderbom and Bai-Yun Zeng
14. Impact of circadian and diurnal rhythms on cellular metabolic function and neurodegenerative diseases
S. Kendall Smith and Erik S. Musiek
15. The impact of neurovascular, blood-brain barrier, and glymphatic dysfunction in neurodegenerative and metabolic diseases
Molly Braun and Jeffrey J. Iliff