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The oxidative metabolism of dopamine and consequent oxidative stress are implicated in dopaminergic neuronal loss, mediating the pathogenesis of Parkinson's disease (PD). The inducible detoxifying antioxidative enzyme Quinone oxidoreductase (NQO1) (NAD(P)H: quinone oxidoreductase 1), neuroprotective to counteract reactive oxidative species, is most prominent in the active stage of the disease and virtually absent at the end stage of the disease. However, the molecular mechanism dictating NQOl expression oscillation remains unclear. Here we show that Akt phosphorylates NQO1 at T128 residues and triggers its polyubiquitination and proteasomal degradation, abrogating its antioxidative effects in PD. Akt binds NQO1 in a phosphorylation-dependent manner. Interestingly, Akt, but not PINK1, provokes NQO1 phosphorylation and polyubiquitination with Parkin as an E3 ligase. Unphosphorylatable NQO1 mutant displays more robust neuroprotective activity than WT NQO1 in suppressing reactive oxidative species and against MPTP-induced dopaminergic cell death, rescuing the motor disorders in both a-synuclein transgenic transgenic male and female mice elicited by the neurotoxin. Thus, our findings demonstrate that blockade of Akt-mediated NQO1 degradation may ameliorate PD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The link between nocturia and aging male symptoms (AMS) has not been scientifically established. This study aimed to measure the degree of severity of AMS that impacts health-related quality of life (HRQoL) in adult males living with nocturia and to determine the predictive values of nocturnal factors on AMS., Methods: This is an extended analysis of new data collected by using the Hong Kong Traditional AMS (HK-AMS) scale and the Cantonese version of the Pittsburgh Sleep Quality Index (PSQI) in a recently published cross-sectional population-based survey., Results: Of the 781 respondents that completed the set of questionnaires, 68% and 61% of men living with nocturia reported clinically significant (at moderate-to-severe levels) somato-vegetative and sexual AMS; the prevalence and severity were increased with advancing nighttime voiding frequency. Age, the Global PSQI score, certain metabolic diseases, the nocturia-specific QoL (NQoL) score and bedtime voiding frequency were found to be significant predictive factors for composite somato-vegetative and sexual AMS., Conclusions: The current findings suggested the inclusion of nocturia when measuring male-specific HRQoL related to aging.

Background: Most prevalence surveys on nocturia have focused on older populations. This study aimed to measure the nocturia prevalence across the full spectrum of male adults living in Hong Kong, where severity and associated quality-of-life (QoL) were also explored., Methods: A cross-sectional population-based survey was conducted in men aged 18 or above using the ICIQ-NQoL Questionnaire., Results: With 1239 respondents at age ranged 18-99, the overall nocturia prevalences were found to be 63.0% (ranged 41.6-84.6% at different age groups) and 31.2% (ranged 13.0-56.3% at different age groups), for ≥1 and ≥2 bedtime voiding episodes, respectively. The chance of nocturia was dramatically increased at age 60 or above while both prevalence and voiding frequency were increased with advancing age. About 83% of the nocturia men experienced one to two voiding episodes per night, but many of them had self-rated their QoL poor or very poor and indicated moderate-to-high bothersome. Younger men at age 18-39 were found to have high prevalence as 41.6% and almost 30% of them rated poor or very poor QoL., Conclusions: Nocturia was not only affecting the older populations but also caused significant bothersome and negative impacts on QoL in younger males.