Fibroblast growth factor-21 alleviates proteasome injury via activation of autophagy flux in Parkinson's disease.

Parkinson's disease (PD) is one of the most common and complex Neurodegeneration, with an inherited metabolic disorder. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in metabolic regulation. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here, we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vitro, proteasome impairment models of PD were utilized. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 µmol/L) for 12 h, then with 50 ng/ml FGF-21 with or without 5 mmol/L of 3-methyladenine.The cells were dissected to assess alterations in autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Our data indicate that FGF21 prevents dopaminergic neuron loss and shows beneficial effects against proteasome impairment induced PD syndrome, indicating it might be a potent candidate for developing novel drugs to deal with PD.

Application Value of Serum Neurofilament Light Protein for Disease Staging in Huntington's Disease.

BACKGROUND: Neurofilament light protein (NfL) has been proven to be a sensitive biomarker for Huntington's disease (HD). However, these studies did not include HD patients at advanced stages or with larger CAG repeats (>50), leading to a knowledge gap of the characteristics of NfL. METHODS: Serum NfL (sNfL) levels were quantified using an ultrasensitive immunoassay. Participants were assessed by clinical scales and 7.0 T magnetic resonance imaging. Longitudinal samples and clinical data were obtained. RESULTS: Baseline samples were available from 110 controls, 90 premanifest HD (pre-HD) and 137 HD individuals. We found levels of sNfL significantly increased in HD compared to pre-HD and controls (both P < 0.0001). The increase rates of sNfL were differed by CAG repeat lengths. However, there was no difference in sNfL levels in manifest HD from early to late stages. In addition, sNfL levels were associated with cognitive measures in pre-HD and manifest HD group, respectively. The increased levels of sNfL were also closely related to microstructural changes in white matter. In the longitudinal analysis, baseline sNfL did not correlate with subsequent clinical function decline. Random forest analysis revealed that sNfL had good power for predicting disease onset. CONCLUSIONS: Although sNfL levels are independent of disease stages in manifest HD, it is still an optimal indicator for predicting disease onset and has potential use as a surrogate biomarker of treatment effect in clinical trials. © 2023 International Parkinson and Movement Disorder Society.

Serum Estradiol Correlates With Benign Paroxysmal Positional Vertigo in Postmenopausal Women.

BACKGROUND: A high incidence of benign paroxysmal positional vertigo (BPPV) is reported in postmenopausal women, and the association between estradiol (E2) deficiency and the occurrence of BPPV was investigated. METHODS: Postmenopausal women with and without BPPV were included from 2016 to 2019, and 1-year follow-up was performed. Serum otolin-1 and E2 levels were assayed before the canalith repositioning treatment. Bone mineral density (BMD) was measured with a dual-energy x-ray absorptiometry scan. Receiver operating characteristic analysis was performed to determine the occurrence of BPPV, and Pearson analysis was performed to indicate the correlation between E2, otolin-1, and BMD. RESULTS: Eighty-six postmenopausal women with BPPV and 80 age-, demographics-, and clinical characteristics-matched normal postmenopausal women were enrolled. Decreased E2 levels, increased otolin-1 levels, and decreased BMD were observed in postmenopausal women with BPPV, and increased BMD and decreased otolin-1 levels were observed in patients with higher levels of serum E2. Receiver operating characteristic analysis revealed that E2, otolin-1, and BMD showed low sensitivity and moderate specificity to determine the occurrence of BPPV. On the other hand, a low correlation coefficient was found between E2 and otolin-1, or BMD. It is worth noting that low E2 levels were found in the relapsed patients with BPPV after a 1-year follow-up. CONCLUSION: E2 deficiency is correlated with the occurrence of BPPV, which may be a potential risk biomarker for postmenopausal women.

miR-30b protects nigrostriatal dopaminergic neurons from MPP(+)-induced neurotoxicity via SNCA.

OBJECTIVE: To explore the function of miR-30b in pathogenesis of Parkinson's disease (PD) and its underlying molecular mechanism. MATERIALS AND METHODS: We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP(+)) as a tool for constructing the PD cell model, using miR-30b mimics or inhibitors to manipulate miR-30b level for an experimental model of acquisition. The cell viability of SH-SY5Y was detected by CCK, and luciferase was used to screen the binding of target genes. The protein levels of SNCA were measured by Western blot. Then, we investigate the changes in pro- and anti-apoptotic markers with or without miR-30b treatment. RESULTS: There was a significant low expression of MiR-30b in MPP(+)-induced cells. SH-SY5Y cell viability was rescued by MiR-30b overexpression. Luciferase experiments showed that MiR-30b may bind to the 3'-UTR side of SNCA and inhibited its expression. By Western blot, the SNCA level was markedly decreased by miR-30b. miR-30b attenuated the upregulation of Bax and the depletion of Bcl-2 induced by MPP(+).