Fibrillar α-synuclein toxicity depends on functional lysosomes.

Neurodegeneration in Parkinson's disease (PD) can be recapitulated in animals by administration of α-synuclein preformed fibrils (PFFs) into the brain. However, the mechanism by which these PFFs induce toxicity is unknown. Iron is implicated in PD pathophysiology, so we investigated whether α-synuclein PFFs induce ferroptosis, an iron-dependent cell death pathway.

Ferroptosis and cell death mechanisms in Parkinson's disease.

Symptoms of Parkinson's disease arise due to neuronal loss in multiple brain regions, especially dopaminergic neurons in the substantia nigra pars compacta. Current therapies aim to restore dopamine levels in the brain, but while these provide symptomatic benefit, they do not prevent ongoing neurodegeneration. Preventing neuronal death is a major strategy for disease-modifying therapies; however, while many pathogenic factors have been identified, it is currently unknown how neurons die in the disease.

Prox 1 in eye degeneration and sensory organ compensation during development and evolution of the cavefish Astyanax.

We have investigated expression of the homeobox gene Prox 1 during eye degeneration and sensory organ compensation in cavefish embryos. The teleost Astyanax mexicanus consists of sighted surface-dwelling forms (surface fish) and several populations of blind cave-dwelling forms (cavefish), which have evolved independently. Eye formation is initiated during cavefish development, but the lens vesicle undergoes apoptosis, and the eye subsequently arrests and degenerates.

Plasma- and cerebrospinal fluid-immunoreactive endothelin-1: effects of nonpeptide endothelin receptor antagonists with diverse affinity profiles for endothelin-A and endothelin-B receptors.

Some endothelin (ET) receptor antagonists have been reported to elevate plasma immunoreactive endothelin-1 (irET-1). However, there is no information regarding the effects of ET receptor antagonists on cerebrospinal fluid (CSF) levels. To better understand the regulation of circulating and CSF ET-1, the effects of several nonpeptide antagonists with high, intermediate, or low affinity at the ETB receptor, as well as the potent ETB selective agonist sarafotoxin 6c (S6c), were characterized and compared.