Mutations or environmental stresses lead to misfolded proteins in neurons and other cells. Misfolded or aggregated proteins must be removed immediately or degraded by ubiquitin proteasome system (UPS). Decades of research have shown that inability to respond to misfolded protein is the major cause of neurodegeneration. Aggregated proteins or proteinopathies perturb mitochondrial function, leading to damaged mitochondria and loss of energy and ultimately death of a cell or neurons. Defects in mitochondrial health accumulate as we age, leading to a wide variety of pathologies including but not limited to metabolic syndromes, neurodegeneration, cardiovascular disease, and cancer.  Ubiquitin E3 ligase is a master regulator of mitochondrial health and could be the target of pharmacological therapeutics to reduce cellular aging and pathologies. Ubiquitin ligases mark damaged mitochondria for degradation (mitophagy) and generation of new mitochondria (mitobiogenesis). Defects in UPS pathway are hallmarks of aging and mitochondrial health plays a key role in the process. Defects in response to misfolded proteins or damaged mitochondria are picked up as unique poly-ubiquitin structure in cells and serum. Myto Health has established a platform to isolate and enrich minute poly-ubiquitinated structure from human blood. The unique poly-ubiquitin structures are identified and correlated with neurodegenerative diseases.