Parkinson's disease (PD) is a progressive neurological disorder, mainly characterized by the progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and by the presence of intracellular inclusions, known as Lewy bodies. Despite SNpc being considered the primary affected region in PD, the neuropathological features are confined solely to the nigro-striatal axis. With disease progression other brain regions are also affected, namely the cerebral cortex, although the spreading of the neurologic damage to this region is still not completely unraveled. Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid that has been shown to have antioxidant properties and to exhibit a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD. Moreover, TUDCA anti-inflammatory properties have been reported in glial cells, making it a prominent therapeutic agent in PD. Here, we used C57BL/6 mice injected with MPTP in a sub-acute paradigm aiming to investigate if the neurotoxic effects of MPTP could be extended to the cerebral cortex. In parallel, we evaluated the anti-oxidant, neuroprotective and anti-inflammatory effects of TUDCA. The anti-inflammatory mechanisms elicited by TUDCA were further dissected in microglia cells. Our results show that MPTP leads to a decrease of ATP and activated AMP-activated protein kinase levels in mice cortex, and to a transient increase in the expression of antioxidant downstream targets of nuclear factor erythroid 2 related factor 2 (Nrf-2), and parkin. Notably, MPTP increases pro-inflammatory markers, while down-regulating the expression of the anti-inflammatory protein Annexin-A1 (ANXA1). Importantly, we show that TUDCA treatment prevents the deleterious effects of MPTP, sustains increased levels of antioxidant enzymes and parkin, and most of all negatively modulates neuroinflammation and up-regulates ANXA1 expression. Additionally, results from cellular models using microglia corroborate TUDCA modulation of ANXA1 synthesis, linking inhibition of neuroinflammation and neuroprotection by TUDCA. 2014). PD is mainly a motor disorder, pathologically characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc), severe striatal dopamine depletion, and by the presence of intracellular inclusions containing aggregates of α-synuclein known as Lewy bodies (

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The 6 min walking test (6MWT) has been largely studied. Less is, however, known about responders and non-responders to pulmonary rehabilitation (PR) in other meaningful activities. We explored responders and non-responders and the predictors of response to PR in the 1 min sit-to-stand test (1 min STS) and the 6MWT and compared both measures in classifying responders. An observational study was conducted with 121 people with chronic obstructive pulmonary disease (COPD). The functional status was assessed before and after PR. Baseline differences between responders and non-responders were tested with Mann–Whitney U, chi-square, or Fisher exact tests. Predictors were explored with binary logistic regressions. Agreement between both measures was assessed with chi-square, Cohen’s kappa, and McNemar tests. There were 54.5% and 57.0% of responders in the 1 min STS and the 6MWT, respectively. The proportion of responders was significantly different (p = 0.048), with a small agreement between the measures (kappa = 0.180; p = 0.048). The baseline 6MWT was the only significant predictor of response in the 6MWT (OR = 0.995; pseudo-r2 = 0.117; p < 0.001). No significant predictors were found for the 1 min STS. A large number of non-responders in terms of functional status exist. The 1 min STS and the 6MWT should not be used interchangeably. Future studies should explore the added benefit of personalizing PR to this outcome and investigate other potential predictors.