Ischemic stroke is a severe medical condition characterized by diminished blood flow to the brain, resulting in a shortage of oxygen and nutrients. During ischemia, neurons surrounding the cerebral in Show more
Ischemic stroke is a severe medical condition characterized by diminished blood flow to the brain, resulting in a shortage of oxygen and nutrients. During ischemia, neurons surrounding the cerebral infarct initiate macroautophagy. However, the implications of this activation for neuronal cell survival are still debated. The identification of new autophagy modulators could aid in understanding autophagy's role in brain ischemia and lay the groundwork for innovative therapeutic strategies aimed at minimizing brain damage in this life-threatening neurological emergency. In this study, we developed a robust and sensitive screening platform to identify autophagy modulators from a library of bioactive compounds. Selected compounds underwent further Show less
Neurodegenerative and inflammatory processes influence the clinical course of multiple sclerosis (MS). The β-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been associated with cognitive Show more
Neurodegenerative and inflammatory processes influence the clinical course of multiple sclerosis (MS). The β-site amyloid precursor protein cleaving enzyme 1 (BACE1) has been associated with cognitive dysfunction, amyloid deposition and neuroinflammation in Alzheimer's disease. We explored in a group of 50 patients with relapsing-remitting MS the association between the cerebrospinal fluid (CSF) levels of BACE1, clinical characteristics at the time of diagnosis and prospective disability after three-years follow-up. In addition, we assessed the correlations between the CSF levels of BACE 1, amyloid β (Aβ) 1-40 and 1-42, phosphorylated tau (pTau), lactate, and a set of inflammatory and anti-inflammatory molecules. BACE1 CSF levels were correlated positively with depression as measured with Beck Depression Inventory-Second Edition scale, and negatively with visuospatial memory performance evaluated by the Brief Visuospatial Memory Test-Revised. In addition, BACE CSF levels were positively correlated with Bayesian Risk Estimate for MS at onset, and with Expanded Disability Status Scale score assessed three years after diagnosis. Furthermore, a positive correlation was found between BACE1, amyloid β 42/40 ratio (Spearman's r = 0.334, p = 0.018, n = 50), pTau (Spearman's r = 0.304, p = 0.032, n = 50) and lactate concentrations (Spearman's r = 0.361, p = 0.01, n = 50). Finally, an association emerged between BACE1 CSF levels and a group of pro and anti-inflammatory molecules, including interleukin (IL)-4, IL-17, IL-13, IL-9 and interferon-γ. BACE1 may have a role in different key mechanisms such as neurodegeneration, oxidative stress and inflammation, influencing mood, cognitive disorders and disability progression in MS. Show less