Naturally Derived Compounds as Preventatives of Proteinopathies

Neurodegenerative diseases, such as Parkinson’s disease (PD), afflict millions worldwide. Of greater concern is the fact that a main risk factor this disease is aging and the baby boomer population is now reaching a geriatric age. Despite the active research in this area, little progress has been made in the development of therapeutic strategies and furthering of our understanding in pinpointing the causal events that onset these disease processes. Our lab has focused on studying the protein homeostasis of key biomarkers in neurodegenerative diseases and examining whether natural compounds can act as neuro-protectants and, thus, attenuate the pathology that ensues in these conditions. First, we sought to determine whether Na-β-hydroxybutyrate (NaβHB) could serve as a prophylactic for PD. We did so by using an organismal, vertebrate model (rat) to induce a Parkinsonian condition via chronic injection of rotenone, a known mitochondrial complex I inhibitor. Animals underwent behavioral testing to ascertain the presence of motor deficits. After the behavioral testing, tissue was collected to perform immunohistochemical analysis. The potential of NaβHB to rescue neurons and protect from damage was determined by counting the number of TH-positive neurons in the Substantia Nigra pars compacta (SNpc). The exact causal agents of Parkinson’s disease and Alzheimer’s disease (AD) are unknown; however, there are biochemical and cellular changes that are common to both, such as: oxidative stress, mitochondrial dysfunction and protein aggregation. Given the commonalities of these two disease processes, we aimed to examine whether we could intercede in the pathogenesis caused by the prion-like protein, β-amyloid (AD associated), when introduced to a non-native environment and allowed to interact with another prion-like protein, α-synuclein. The molecule of choice was Tanshinone IIA, a polyphenol found in red sage, which has the potential to scavenge free radicals and has shown promise in other areas of biomedical research