Tau protein—a member of the microtubule-associated protein family—is a key protein involved in many neurodegenerative diseases. Tau pathology in neurodegenerative diseases is characterized by pathological tau aggregation in neurofibrillary tangles (NFTs). Diseases with this typical pathological feature are called tauopathies. Parkinson's disease (PD) was not initially considered to be a typical tauopathy. However, recent studies have demonstrated increasing evidence of tau pathology in PD. A genome-wide association (GWA) study indicated a potential association between tauopathy and sporadic PD. The aggregation and deposition of tau were also observed in ~50% of PD brains, and it seems to be transported from neuron to neuron. The aggregation of NFTs, the abnormal hyperphosphorylation of tau protein, and the interaction between tau and alpha-synuclein may all contribute to the cell death and poor axonal transport observed in PD and Parkinsonism.

Chronic rhinosinusitis with nasal polyps (CRSwNP), one of the most prevalent chronic diseases, is characterized by persistent inflammation of sinonasal mucosa. However, the pathogenesis of CRSwNP remains unclear. Here, we performed next-generation RNA sequencing and a comprehensive bioinformatics analyses to characterize the transcriptome profiles, including mRNAs and long noncoding RNAs (lncRNAs), in patients with eosinophilic and noneosinophilic CRSwNP. A total of 1917 novel lncRNAs and 280 known lncRNAs were identified. We showed eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (non-ECRSwNP) display distinct transcriptome profiles. We identified crucial pathways, including inflammatory, immune response and extracellular microenvironment, connected to the pathogenetic mechanism of CRSwNP. We also discovered key lncRNAs differentially expressed, including lncRNA XLOC_010280, which regulates CCL18 and eosinophilic inflammation. The qRT-PCR and in situ RNA hybridization results verified the key differentially expressed genes. The feature of distinct transcriptomes between ECRSwNP and non-ECRSwNP suggests the necessity to develop specific biomarkers and personalized therapeutic strategies. Our findings lay a solid foundation for subsequent functional studies of mRNAs and lncRNAs as diagnostic and therapeutic targets in CRSwNP by providing a candidate reservoir.

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder. Recent studies have implicated a role for peroxisome proliferator-activated receptor γ coactivator protein-1α (PGC-1α) in PD and in animal or cellular models of PD. The role of PGC-1α in the function and survival of substantia nigra pars compacta (SNpc) dopamine neurons is not clear. Here we find that there are four different PGC-1α isoforms expressed in SH-SY5Y cells, and these four isoforms are expressed across subregions of mouse brain. Adult conditional PGC-1α knock-out mice show a significant loss of dopaminergic neurons that is accompanied by a reduction of dopamine in the striatum. In human PD postmortem tissue from the SNpc, there is a reduction of PGC-1α isoforms and mitochondria markers. Our findings suggest that all four isoforms of PGC-1α are required for the proper expression of mitochondrial proteins in SNpc DA neurons and that PGC-1α is essential for SNpc DA neuronal survival, possibly through the maintenance of mitochondrial function.

Background: The ligands of mitochondrial translocator protein (TSPO) have been widely used as diagnostic biomarkers for glioma. However, the true biological actions of TSPO in vivo and its role in glioma tumorigenesis remain elusive. Methods: TSPO knockout xenograft and spontaneous mouse glioma models were employed to assess the roles of TSPO in the pathogenesis of glioma. A Seahorse Extracellular Flux Analyzer was used to evaluate mitochondrial oxidative phosphorylation and glycolysis in TSPO knockout and wild-type glioma cells. Results: TSPO deficiency promoted glioma cell proliferation in vitro in mouse GL261 cells and patient-derived stem cell–like GBM1B cells. TSPO knockout increased glioma growth and angiogenesis in intracranial xenografts and a mouse spontaneous glioma model. Loss of TSPO resulted in a greater number of fragmented mitochondria, increased glucose uptake and lactic acid conversion, decreased oxidative phosphorylation, and increased glycolysis. Conclusion: TSPO serves as a key regulator of glioma growth and malignancy by controlling the metabolic balance between mitochondrial oxidative phosphorylation and glycolysis. 1. TSPO deficiency promotes glioma growth and angiogenesis. 2. TSPO regulates the balance between mitochondrial oxidative phosphorylation and glycolysis.

Neurons affected in Parkinson’s disease (PD) experience mitochondrial dysfunction and bioenergetic deficits that occur early and promote the disease-related α-synucleinopathy. Emerging findings suggest that the autophagy-lysosome pathway, which removes damaged mitochondria (mitophagy), is also compromised in PD and results in the accumulation of dysfunctional mitochondria. Studies using genetic and toxin-induced animal and cellular models as well as postmortem human tissue indicate that impaired mitophagy might play a critical role in the pathogenesis of synaptic dysfunction and the aggregation of misfolded proteins, which in turn impairs mitochondrial homeostasis. Interventions that stimulate mitophagy to maintain mitochondrial health might therefore be used as an approach to delay the neurodegenerative processes in PD.