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Heme oxygenase‐1 (HO‐1) is the only way for cells to decompose heme. It can cleave heme to produce carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin (BV). BV is reduced to bilirubin (BR) by biliverdin reductase(BVR). In previous studies, HO‐1 was considered to have protective effects because of its anti‐inflammatory, anti‐apoptosis, and antiproliferation functions. However, emerging experimental studies have found that the metabolites derived from HO‐1 can cause increase iin intracellular oxidative stress, mitochondrial damage, iron death, and autophagy. Because of its particularity, it is very meaningful to understand its exact mechanism. In this review, we summarized the protective and toxic effects of HO‐1, its potential mechanism, its role in neurodegenerative diseases and related drug research. This knowledge may be beneficial to the development of new therapies for neurodegenerative diseases and is crucial to the development of new therapeutic strategies and biomarkers. [ABSTRACT FROM AUTHOR]

As a pathological biomarker of Parkinson's disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on SNCAA53T transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; however, it appears to be difficult to clear it from the brain in a short period of time. [ABSTRACT FROM AUTHOR]

Introduction: Alpha-synuclein (αSyn) is believed to play a central role in the pathogenesis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) total αSyn were significantly lower in PD patients, whereas the aggregates were higher, and this phenomenon was further exacerbated with longer disease duration. However, whether CSF αSyn can be the cause and/or a consequence in PD is not fully elucidated., Method: We administered 2 ng or 200 ng αSyn preformed fibrils (PFFs) by intracerebroventricular injection for consecutive 7 days in C57BL/6 mice. The olfactory function was assessed by the olfactory discrimination test and buried food-seeking test. The locomotor function was assessed by the rotarod test, pole test, open field test and CatWalk gait analysis. Phosphorylated αSyn at serine 129 was detected by the immunohistochemistry staining. Iron levels was determined by Perl's-diaminobenzidine iron staining and synchrotron-based X-ray fluorescence., Results: The mice did not exhibit any diffuse synucleinopathy in the brain for up to 30 weeks, although αSyn PFFs induced aggregation in SH-SY5Y cells and in the substantia nigra and striatum of mice with stereotactic injection. No impairment of motor behaviors or olfactory functions were observed, although there was a temporary motor enhancement at 1 week. We then demonstrated iron levels were comparable in certain brain regions, suggesting there was no iron deposition/redistribution occurred., Conclusion: The intraventricular injection of αSyn PFFs does not induce synucleinopathy or behavioral symptoms. These findings have implications that CSF αSyn aggregates may not necessarily contribute to the onset or progression in PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

With the intensification of aging population, the prevention or treatment of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, has drawn more and more attention. As a long used traditional Chinese medicine, Uncaria rhynchophylla (Miq.) Jacks., named Gouteng in Chinese, has been reported to have an effective neuroprotective role in neurodegenerative diseases. In this review, the beneficial pharmacological effects and signaling pathways of herbal formulas containing U. rhynchophylla, especially major compounds identified from U. rhynchophylla , such as corynoxine B, corynoxine, rhynchophylline, and isorhynchophylline, in neurodegenerative diseases, were summarized, which not only provide an overview of U. rhynchophylla for the prevention or treatment of neurodegenerative diseases but also give some perspective to the development of new drugs from traditional Chinese medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Liu and Xie.)