Molecular mechanism of prion-like tau-induced neurodegeneration.
Alonso Alejandra D,Beharry Cindy,Corbo Christopher P,Cohen Leah S
Alzheimer's & dementia : the journal of the Alzheimer's Association
INTRODUCTION:Accumulation of hyperphosphorylated tau and the disruption of microtubules are correlated with synaptic loss and pathology of Alzheimer's disease (AD). Impaired cognitive function and pathology of AD is correlated with this lesion. This review looks at the mechanism of neurodegeneration, the prion-like behavior of tau in its interaction with normal MAPs in correlation with tau hyperphosphorylation. METHODS:We reviewed our work in the field as well as current literature that pertains to tau phosphorylation and the biological effects. RESULTS:Hyperphosphorylation of tau in AD, in vitro, in cells, or in animal models converts this protein into a prion-like protein that is able to propagate the altered conformation. DISCUSSION:These findings suggest that phosphorylation of tau is a critical event in neurodegeneration. The combination of phosphorylation sites can generate a gain of toxic function for tau. The mechanism of tau toxicity might involve not only the microtubule system but also interference with other cellular compartments such as the nucleus and the actin cytoskeleton.
Mechanism of Neonicotinoid Toxicity: Impact on Oxidative Stress and Metabolism.
Wang Xu,Anadón Arturo,Wu Qinghua,Qiao Fang,Ares Irma,Martínez-Larrañaga María-Rosa,Yuan Zonghui,Martínez María-Aránzazu
Annual review of pharmacology and toxicology
Thousands of tons of neonicotinoids are widely used around the world as broad-spectrum systemic insecticides and veterinary drugs. Researchers originally thought that neonicotinoids exhibited low mammalian toxicity. However, following their widespread use, it became increasingly evident that neonicotinoids could have various toxic effects on vertebrates and invertebrates. The primary focus of this review is to summarize the research progress associated with oxidative stress as a plausible mechanism for neonicotinoid-induced toxicity as well as neonicotinoid metabolism. This review summarizes the research conducted over the past decade into the production of reactive oxygen species, reactive nitrogen species, and oxidative stress as aresult of neonicotinoid treatments, along with their correlation with the toxicity and metabolism of neonicotinoids. The metabolism of neonicotinoids and protection of various compounds against neonicotinoid-induced toxicity based on their antioxidative effects is also discussed. This review sheds new light on the critical roles of oxidative stress in neonicotinoid-induced toxicity to nontarget species.