The lower urinary tract symptoms (LUTSs) and acute urinary retention (AUR) caused by benign prostatic hyperplasia (BPH) can seriously affect the quality of life of elderly men. Studies suggest that both androgens and inflammation greatly influence the occurrence and development of BPH in most patients. These two factors combined can also affect each other, leading to pathological changes in the stromal and epithelial tissue of the prostate transition zone in BPH patients. DHT in the prostate tissue of BPH patients may activate a chronic inflammatory response in the prostate, amplifying the expression of inflammatory factors and upregulating the proliferation ability of prostate tissue.

Parkinson’s disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1β, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT–GSK-3β and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP⁺ or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation.

Androgens and chronic inflammation, which play essential roles in the development of benign prostatic hyperplasia (BPH), are considered to be important factors in disorders of prostate homeostasis. These two factors may lead to pathological hyperplasia in the prostate transition zone of patients with BPH. However, few studies have examined the mechanism of how dihydrotestosterone (DHT) affects chronic inflammation in prostate tissue during the progression of BPH. This study examined the performance of DHT in lipopolysaccharide-treated M1 macrophages and the subsequent effects on the proliferation of prostate stromal and epithelial cells. We found that DHT increased secretion of the pro-inflammatory factor tumor necrosis factor (TNF)-α from M1 macrophages differentiated from THP-1 cells. The supernatant of M1 macrophages promoted the proliferation of WPMY-1 prostate stromal cells by upregulating B-cell lymphoma-extra large (Bcl-xL) and cellular Myc (c-Myc) levels by activating TNF-α-mediated nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, this supernatant increased the expression of androgen receptor in WPMY-1 cells, which was TNF-α-independent. Additionally, TNF-α protein expression was significantly higher in patients with BPH and a large prostate volume than that in those with a small prostate volume. Further analysis showed that higher serum testosterone combined with prostate-specific androgen concentrations was related to TNF-α expression. This study suggests that DHT modulates the inflammatory environment of BPH by increasing TNF-α expression from lipopolysaccharide-treated M1 macrophages and promotes the proliferation of prostate stromal cells. Targeting TNF-α, but not DHT, may be a promising strategy for patients with BPH.

The age-related androgens depletion has been implicated in compromised neuroprotection and is involved in the pathogenesis of neurodegenerative disease including Alzheimer’s disease (AD), the leading cause of dementia. Emerging data revealed that reduction of both serum and brain androgen levels in male is associated with increased amyloid-beta (Aβ) accumulation, a putative cause of AD. It has been demonstrated that androgens can function as the endogenous negative regulators of Aβ. However, the mechanisms by which androgens regulate Aβ production, degradation and clearance, as well as Aβ-induced pathological process in AD are still elusive. This review emphasizes the contributions of androgen to the Aβ metabolism and toxicity in AD and thus may provide novel strategies for prevention and therapeutics.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder accompanied by neuroinflammation. Many studies have demonstrated that interleukin-6 (IL-6) exhibits both anti-inflammatory and pro-inflammatory effects in the central nervous system, yet its role in PD remains controversial. In this study, Il6^−/− (knockout), Il6^+/−, and wild-type mice were utilized to investigate the impact of IL-6 on the pathology of MPTP- or α-Synuclein^A53T-induced PD mice. Our findings revealed that Il6 deficiency exacerbated motor dysfunction in both female and male mice. MPTP intoxication resulted in earlier and more extensive injuries to the dopaminergic system and heightened glial reaction in the nigrostriatal pathway of female Il6^−/− mice compared with male Il6^−/− mice, which only displayed more severe dopaminergic neuronal loss at 7 days after MPTP administration. Toxic α-Synuclein overexpression in the substantia nigra region caused earlier motor dysfunction and aggravated dopaminergic neurodegeneration in female Il6^−/− mice. In Il6^+/− mice, MPTP-induced depletion of dopaminergic nerve fibers was unaffected, although astrocyte activation was attenuated. Moreover, intraperitoneal administration of recombinant IL-6 (rIL-6) partially ameliorated MPTP-induced motor dysfunction and striatal dopaminergic terminal depletion in both wild-type and knockout mice. Our findings underscore the crucial role of IL-6 in the inflammatory pathology of PD, highlighting sex-dependent differences, and suggest that rIL-6 holds potential promise for PD therapy.