九州大学 · 医学
Junjun Ni教授の研究室では、神経変性疾患、特にアルツハイマー病におけるアミロイドベータの蓄積と神経炎症のメカニズムに注目し、リソソーム関連酵素であるカテプシンB(CatB)の役割を解明しています。特に、慢性炎症や酸化的ストレスが神経変性を促進するメカニズムとして、マクロファージ・ミクログリアにおけるCatBのプロテアーゼシグナル伝達が鍵を握っているとされています。また、口腔・腸内微生物と脳の関連性や、天然物(グリーンプロポリス)の神経保護作用についても、神経機能の維持・回復をめざした基盤的研究を展開しています。
Figures are computed from collected data and may differ slightly.
Cathepsin B (CatB), a cysteine protease, is primarily localized within subcellular endosomal and lysosomal compartments. It is involved in the turnover of intracellular and extracellular proteins. Interest is growing in CatB due to its diverse roles in physiological and pathological processes. In functional defective tissues, programmed cell death (PCD) is one of the regulable fundamental mechanisms mediated by CatB, including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell
Proteinase cascades are part of the basic machinery of neuronal death pathways. Neuronal cathepsin B (CatB), a typical cysteine lysosomal protease, plays a critical role in neuronal death through lysosomal leakage or excessive autophagy. On the other hand, much attention has been paid to microglial CatB in neuronal death. We herein show the critical role of proteolytic relay through microglial CatB and CatE in the polarization of microglia/macrophages in the neurotoxic phenotype, leading to hypo
Alzheimer's disease (AD) is one of the most frequently diagnosed neurodegenerative disorders worldwide and poses a major challenge for both affected individuals and their caregivers. AD is a progressive neurological disorder associated with high rates of brain atrophy. Despite its durable influence on human health, understanding AD has been complicated by its enigmatic and multifactorial nature. Neurofibrillary tangles and the deposition of amyloid-beta (Aβ) protein are typical pathological feat
Abnormal accumulation of amyloid-β (Aβ) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aβ in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aβ is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aβ metabolism
During normal aging, innate immunity progresses to a chronic state. However, how oxidative stress and chronic neuroinflammation arise during aging remains unclear. In this study, we found that genetic ablation of cathepsin B (CatB) in mice significantly reduced the generation of reactive oxygen species (ROS) and neuroinflammation and improved cognitive impairment during aging. In cultured microglia, pharmacological inhibition of CatB significantly reduced the generation of mitochondria-derived R
Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer's disease (AD). We have found that Brazilian green propolis (propolis) improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF),
Clock gene disturbance in microglia is involved in the early onset of AD through the induction of chronic neuroinflammation, which may be a new target for preventing or slowing AD.
Cathepsin B (CatB) is a typical cysteine lysosomal protease involved in a variety of physiologic and pathological processes. It is expressed in most cell types and is primarily localized within subcellular endosomal and lysosomal compartments. Emerging scientific evidence indicates that lysosomal leaked CatB is involved in mitochondrial stress, inflammasome activation, and nuclear senescence, but without the acidic environment. CatB is also secreted as a myokine, which is involved in muscle-brai
Lung cancer is one of the most prevalent types of cancer, but accurate diagnosis remains a challenge. The aim of the present study was to create a model using amino acids and acylcarnitines for lung cancer screening. Serum samples were obtained from two groups of patients with lung cancer recruited in 2015 (including 40 patients and 100 matched controls) and 2017 (including 17 patients and 30 matched controls). Using a metabolomics method, 21 metabolites (13 types of amino acids and 8 types of a
The current trend for the rapid growth of the global aging population poses substantial challenges for society. The human aging process has been demonstrated to be closely associated with changes in gut microbiota composition, diversity, and functional features. During the first 2 years of life, the gut microbiota undergoes dramatic changes in composition and metabolic functions as it colonizes and develops in the body. Although the gut microbiota is nearly established by the age of three, it co
These findings demonstrated that chronic systemic exposure to P gLPS simultaneously induces inflammation-dependent bone loss and AD-like pathologies by elevating IL-6 and IL-17 from middle age, suggesting that periodontal bacteria induce exacerbation of bone loss and memory decline, resulting in AD progression.
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