Metabolic dysfunctions in the intranigral rotenone model of Parkinson's disease.

Parkinson disease (PD) is a chronic neurodegenerative disorder characterized by a progressive loss of dopamine neurons in the substantia nigra pars compacta (SNpc). In the last years, a growing interest to study the relationship between metabolic dysfunction and neurodegenerative disease like PD has emerged. This study aimed to evaluate the occurrence of possible changes in metabolic homeostasis due to intranigral rotenone administration, a neurotoxin that damages dopaminergic neurons leading to motor impairments mimicking those that happen in PD. Male Wistar rats were distributed into two groups: sham (n = 10) or rotenone (n = 10). Sham group received, bilaterally, within the SNpc, 1 µL of vehicle dimethyl-sulfoxide (DMSO) and the experimental group was bilaterally injected with 1 µL of rotenone (12 µg/µL). Twenty-four hours after the stereotaxic surgeries, the animals underwent the open field test followed by subsequent peripheral blood and cerebrospinal fluid (CSF) samples collection for biochemical testing. The results showed that rotenone was able to replicate the typical motor behavior impairment seen in the disease, i.e., decrease in locomotion (P = 0.05) and increase in immobility (P = 0.01) with a strong correlation (r = - 0.85; P < 0.0001) between them. In addition, it was demonstrated that this model is able to decrease plasmatic total-cholesterol (P = 0.04) and HDL-cholesterol (P = 0.007) potentially impacting peripheral metabolism. Hence, it was revealed a potential ability to reproduce relevant metabolic dysfunctions like hyperglycemia which could be explained by acute and systemic mitochondrial rotenone toxicity and SNpc nigral toxicity. Such mechanisms may still be responsible for the potential occurrence of CSF-hyperglycemia (d = 0.7). Since intranigral rotenone is an early phase model of PD, the present results open a new road for studies aiming to investigate metabolic changes in PD.

The multiple functions of the co-chaperone stress inducible protein 1.

Stress inducible protein 1 (STI1) is a co-chaperone acting with Hsp70 and Hsp90 for the correct client proteins' folding and therefore for the maintenance of cellular homeostasis. Besides being expressed in the cytosol, STI1 can also be found both in the cell membrane and the extracellular medium playing several relevant roles in the central nervous system (CNS) and tumor microenvironment. During CNS development, in association with cellular prion protein (PrPc), STI1 regulates crucial events such as neuroprotection, neuritogenesis, astrocyte differentiation and survival. In cancer, STI1 is involved with tumor growth and invasion, is undoubtedly a pro-tumor factor, being considered as a biomarker and possibly therapeutic target for several malignancies. In this review, we discuss current knowledge and new findings on STI1 function as well as its role in tissue homeostasis, CNS and tumor progression.