Research progress of cathepsin B in brain aging and Alzheimer’s diseases
Received date: 2022-12-26
Revised date: 2023-02-15
Online published: 2023-02-21
Supported by
the National Natural Science Foundation of China(32070954);Beijing Natural Science Foundation(7212066)
Cathepsin B (CatB), a cysteine protease derived from lysosomes, was initially thought to non-selectively degrade proteins from phagocytosis and autophagy in lysosomes. However, CatB has been demonstrated to selectively degrade and specifically activate target proteins, thereby regulating the process of physiological and pathological responses. The expression, enzymatic activity, and cellular localization of CatB are significantly altered in brain aging and age-related neurodegenerative diseases. Therefore, the pathological function of CatB has attracted much attention in neuroscience research. In this review, we systematically summarize the molecular functions of CatB in brain aging and Alzheimer’s disease and discuss the current problems in neuropathological studies of CatB, which lay a foundation for a comprehensive understanding of the pathogenesis of aging and Alzheimer’s disease.
Key words： cathepsin B; aging; Alzheimer’s disease; microglia; neuron
Xiaokang Shang, Simeng Zhang, Junjun Ni . Research progress of cathepsin B in brain aging and Alzheimer’s diseases[J]. Hereditas(Beijing), 2023 , 45(3) : 212 -220 . DOI: 10.16288/j.yczz.22-422
| [1] | Ni JJ, Lan F, Xu Y, Nakanishi H, Li X. Extralysosomal cathepsin B in central nervous system: mechanisms and therapeutic implications. Brain Pathol, 2022, 32(5): e13071. |
| [2] | Musil D, Zucic D, Turk D, Engh RA, Mayr I, Huber R, Popovic T, Turk V, Towatari T, Katunuma N. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J, 1991, 10(9): 2321-2330. |
| [3] | Illy C, Quraishi O, Wang J, Purisima E, Vernet T, Mort JS. Role of the occluding loop in cathepsin B activity. J Biol Chem, 1997, 272(2): 1197-1202. |
| [4] | Mijanovi? O, Brankovi? A, Panin AN, Savchuk S, Timashev P, Ulasov I, Lesniak MS. Cathepsin B: a sellsword of cancer progression. Cancer Lett, 2019, 449: 207-214. |
| [5] | Schechter I, Berger A.On the size of the active site in proteases. I. Papain. 1967. Biochem Biophys Res Commun, 2012, 425(3): 497-502. |
| [6] | Gosalia DN, Salisbury CM, Ellman JA, Diamond SL. High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays. Mol Cell Proteomics, 2005, 4(5): 626-636. |
| [7] | Choe Y, Leonetti F, Greenbaum DC, Lecaille F, Bogyo M, Br?mme D, Ellman JA, Craik CS. Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities. J Biol Chem, 2006, 281(18): 12824-12832. |
| [8] | Howie AJ, Burnett D, Crocker J. The distribution of cathepsin B in human tissues. J Pathol, 1985, 145(4): 307-314. |
| [9] | Bernstein HG, Kirschke H, Wiederanders B, Schmidt D, Rinne A. Antigenic expression of cathepsin B in aged human brain. Brain Res Bull, 1990, 24(4): 543-549. |
| [10] | Nakamura Y, Takeda M, Suzuki H, Hattori H, Tada K, Hariguchi S, Hashimoto S, Nishimura T. Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease. Neurosci Lett, 1991, 130(2): 195-198. |
| [11] | Hook G, Jacobsen JS, Grabstein K, Kindy M, Hook V. Cathepsin B is a new drug target for traumatic brain injury therapeutics: evidence for E64d as a promising lead drug candidate. Front Neurol, 2015, 6: 178. |
| [12] | Erdel M, Trefz G, Spiess E, Habermaas S, Spring H, Lah T, Ebert W. Localization of cathepsin B in two human lung cancer cell lines. J Histochem Cytochem, 1990, 38(9): 1313-1321. |
| [13] | Uchiyama Y, Nakajima M, Watanabe T, Waguri S, Sato N, Yamamoto M, Hashizume Y, Kominami E. Immunocytochemical localization of cathepsin B in rat anterior pituitary endocrine cells, with special reference to its co-localization with renin and prorenin in gonadotrophs. J Histochem Cytochem, 1991, 39(9): 1199-1205. |
| [14] | Hernandez ML, Marone M, Gorse KM, Lafrenaye AD. Cathepsin B relocalization in late membrane disrupted neurons following diffuse brain injury in rats. ASN Neuro, 2022, 14: 17590914221099112. |
| [15] | Cavallo-Medved D, Moin K, Sloane B. Cathepsin B: basis sequence: mouse. AFCS Nat Mol Pages, 2011, 2011: A000508. |
| [16] | Lakka SS, Gondi CS, Yanamandra N, Olivero WC, Dinh DH, Gujrati M, Rao JS. Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis. Oncogene, 2004, 23(27): 4681-4689. |
| [17] | Roberts LR, Kurosawa H, Bronk SF, Fesmier PJ, Agellon LB, Leung WY, Mao F, Gores GJ. Cathepsin B contributes to bile salt-induced apoptosis of rat hepatocytes. Gastroenterology, 1997, 113(5): 1714-1726. |
| [18] | Ni JJ, Wu Z, Stoka V, Meng J, Hayashi Y, Peters C, Qing H, Turk V, Nakanishi H. Increased expression and altered subcellular distribution of cathepsin B in microglia induce cognitive impairment through oxidative stress and inflammatory response in mice. Aging Cell, 2019, 18(1): e12856. |
| [19] | Meng J, Liu YC, Xie Z, Qing H, Lei P, Ni JJ. Nucleus distribution of cathepsin B in senescent microglia promotes brain aging through degradation of sirtuins. Neurobiol Aging, 2020, 96: 255-266. |
| [20] | Blinkouskaya Y, Ca?oilo A, Gollamudi T, Jalalian S, Weickenmeier J. Brain aging mechanisms with mechanical manifestations. Mech Ageing Dev, 2021, 200: 111575. |
| [21] | Isaev NK, Stelmashook EV, Genrikhs EE, Oborina MV, Kapkaeva MR, Skulachev VP. Alzheimer's disease: an exacerbation of senile phenoptosis. Biochemistry (Mosc), 2015, 80(12): 1578-1581. |
| [22] | Patterson SL. Immune dysregulation and cognitive vulnerability in the aging brain: interactions of microglia, IL-1β, BDNF and synaptic plasticity. Neuropharmacology, 2015, 96(Pt A):11-18. |
| [23] | Yuan J, Cai SQ. The regulatory mechanisms of behavioral and cognitive aging. Hereditas(Beijing), 2021, 43(6): 545-570. |
| [23] | 袁洁, 蔡时青. 衰老过程中行为和认知功能退化的调控机制研究. 遗传, 2021, 43(6): 545-570. |
| [24] | Burns A, Iliffe S. Alzheimer's disease. BMJ, 2009, 338: b158. |
| [25] | Xiong WD, Xu KY, Lu L, Li JL. Research progress on lncRNAs in Alzheimer's disease. Hereditas(Beijing), 2022, 44(3): 189-197. |
| [25] | 熊婉迪, 徐开宇, 陆林, 李家立. 长链非编码RNA在阿尔茨海默病中的研究进展.遗传, 2022, 44(3): 189-197. |
| [26] | Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, Hammers A, Tai YF, Fox N, Kennedy A, Rossor M, Brooks DJ. Microglia, amyloid, and cognition in Alzheimer's disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis, 2008, 32(3): 412-419. |
| [27] | McGeer EG, McGeer PL. Neuroinflammation in Alzheimer's disease and mild cognitive impairment: a field in its infancy. J Alzheimers Dis, 2010, 19(1): 355-361. |
| [28] | Takahashi RH, Almeida CG, Kearney PF, Yu FM, Lin MT, Milner TA, Gouras GK. Oligomerization of Alzheimer's beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci, 2004, 24(14): 3592-3599. |
| [29] | Gouras GK, Tampellini D, Takahashi RH, Capetillo-Zarate E. Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer's disease. Acta Neuropathol, 2010, 119(5): 523-541. |
| [30] | Goedert M, Spillantini MG. A century of Alzheimer's disease. Science, 2006, 314(5800): 777-781. |
| [31] | Gao Y, Tan L, Yu JT, Tan L. Tau in Alzheimer's disease: mechanisms and therapeutic strategies. Curr Alzheimer Res, 2018, 15(3): 283-300. |
| [32] | Spittau B. Aging microglia-phenotypes, functions and implications for age-related neurodegenerative diseases. Front Aging Neurosci, 2017, 9: 194. |
| [33] | Leng FD. Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nat Rev Neurol, 2021, 17(3): 157-172. |
| [34] | Harry GJ. Microglia during development and aging. Pharmacol Ther, 2013, 139(3): 313-326. |
| [35] | Tremblay Mè, Zettel ML, Ison JR, Allen PD, Majewska AK. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices. Glia, 2012, 60(4): 541-558. |
| [36] | von Bernhardi R, Eugenín-von Bernhardi L, Eugenín J. Microglial cell dysregulation in brain aging and neurodegeneration. Front Aging Neurosci, 2015, 7: 124. |
| [37] | Nakanishi H. Neuronal and microglial cathepsins in aging and age-related diseases. Ageing Res Rev, 2003, 2(4): 367-381. |
| [38] | Islam MI, Nagakannan P, Shcholok T, Contu F, Mai S, Albensi BC, Del Bigio MR, Wang JF, Sharoar MG, Yan RQ, Park IS, Eftekharpour E. Regulatory role of cathepsin L in induction of nuclear laminopathy in Alzheimer's disease. Aging Cell, 2022, 21(1): e13531. |
| [39] | Amano T, Nakanishi H, Kondo T, Tanaka T, Oka M, Yamamoto K. Age-related changes in cellular localization and enzymatic activities of cathepsins B, L and D in the rat trigeminal ganglion neuron. Mech Ageing Dev, 1995, 83(3): 133-141. |
| [40] | Nakanishi H, Wu Z. Microglia-aging: roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging. Behav Brain Res, 2009, 201(1): 1-7. |
| [41] | Nakanishi H. Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging. Neural Regen Res, 2020, 15(1): 25-29. |
| [42] | Pan YF, Wang YY, Chen JW, Fan YM. Mitochondrial metabolism's effect on epigenetic change and aging. Hereditas(Beijing), 2019, 41(10): 893-904. |
| [42] | 潘云枫, 王演怡, 陈静雯, 范怡梅. 线粒体代谢介导的表观遗传改变与衰老研究. 遗传, 2019, 41(10): 893-904. |
| [43] | Arantes RME, Andrews NW. A role for synaptotagmin VII-regulated exocytosis of lysosomes in neurite outgrowth from primary sympathetic neurons. J Neurosci, 2006, 26(17): 4630-4637. |
| [44] | Padamsey Z, McGuinness L, Bardo SJ, Reinhart M, Tong RD, Hedegaard A, Hart ML, Emptage NJ. Activity- dependent exocytosis of lysosomes regulates the structural plasticity of dendritic spines. Neuron, 2017, 93(1): 132-146. |
| [45] | Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G, Janke E, Lubejko ST, Greig NH, Mattison JA, Duzel E, van Praag H. Running-induced systemic cathepsin B secretion is associated with memory function. Cell Metab, 2016, 24(2): 332-340. |
| [46] | Hook V, Yoon M, Mosier C, Ito G, Podvin S, Head BP, Rissman R, O'Donoghue AJ, Hook G. Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders. Biochim Biophys Acta Proteins Proteom, 2020, 1868(8): 140428. |
| [47] | Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, Pfister HW, Fontana A, Hammerschmidt S, Koedel U. The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J Immunol, 2011, 187(10): 5440-5451. |
| [48] | Ruff RL, Secrist D. Inhibitors of prostaglandin synthesis or cathepsin B prevent muscle wasting due to sepsis in the rat. J Clin Invest, 1984, 73(5): 1483-1486. |
| [49] | Terada K, Yamada J, Hayashi Y, Wu Z, Uchiyama Y, Peters C, Nakanishi H. Involvement of cathepsin B in the processing and secretion of interleukin-1beta in chromogranin A-stimulated microglia. Glia, 2010, 58(1): 114-124. |
| [50] | Li JL, Li J, Wang H. Age-associated proteostasis collapse. Hereditas (Beijing), 2022, 44(9): 733-744. |
| [50] | 黎嘉丽, 李瑾, 汪虎. 衰老相关的蛋白稳态失衡. 遗传, 2022, 44(9): 733-744. |
| [51] | Hemonnot AL, Hua J, Ulmann L, Hirbec H. Microglia in Alzheimer disease: well-known targets and new opportunities. Front Aging Neurosci, 2019, 11: 233. |
| [52] | Wu Z, Ni JJ, Liu YC, Teeling JL, Takayama F, Collcutt A, Ibbett P, Nakanishi H. Cathepsin B plays a critical role in inducing Alzheimer's disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice. Brain Behav Immun, 2017, 65: 350-361. |
| [53] | Wang C, Sun BG, Zhou YG, Grubb A, Gan L. Cathepsin B degrades amyloid-β in mice expressing wild-type human amyloid precursor protein. J Biol Chem, 2012, 287(47): 39834-39841. |
| [54] | Mueller-Steiner S, Zhou YG, Arai H, Roberson ED, Sun BG, Chen J, Wang X, Yu GQ, Esposito L, Mucke L, Gan L. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron, 2006, 51(6): 703-714. |
| [55] | Sen A, Capelli V, Husain M. Cognition and dementia in older patients with epilepsy. Brain, 2018, 141(6): 1592-1608. |
| [56] | Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht- Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol, 2003, 56(4): 315-327. |
| [57] | Sun YX, Dai DK, Liu R, Wang T, Luo CL, Bao HJ, Yang R, Feng XY, Qin ZH, Chen XP, Tao LY. Therapeutic effect of SN50, an inhibitor of nuclear factor-κB, in treatment of TBI in mice. Neurol Sci, 2013, 34(3): 345-355. |
| [58] | Kominami E, Tsukahara T, Bando Y, Katunuma N. Distribution of cathepsins B and H in rat tissues and peripheral blood cells. J Biochem, 1985, 98(1): 87-93. |
| [59] | Hook GR, Yu J, Sipes N, Pierschbacher MD, Hook V, Kindy MS. The cysteine protease cathepsin B is a key drug target and cysteine protease inhibitors are potential therapeutics for traumatic brain injury. J Neurotrauma, 2014, 31(5): 515-529. |
| [60] | Luo CL, Chen XP, Yang R, Sun YX, Li QQ, Bao HJ, Cao QQ, Ni H, Qin ZH, Tao LY. Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway. J Neurosci Res, 2010, 88(13): 2847-2858. |
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
