Journal of experimental neurology最新文献_第5页

Impact of Cellular Senescence on Neurodegenerative Diseases during the COVID-19 Pandemic: Sui table Targets Required to Eliminate Cellular Senescence 新冠肺炎大流行期间细胞衰老对神经退行性疾病的影响：消除细胞衰老所需的指标

Journal of experimental neurology

Pub Date : 2021-10-10 DOI: 10.33696/neurol.2.046

M. Mohiuddin, K. Kasahara

We recently reviewed the scientific literature that elucidates the impact of cellular senescence on COVID-19 complications [1]. Recent studies have discussed the association of cellular senescence in COVID-19 patients with neurodegenerative diseases [2-5]. Therefore, in the present study, we extend this scientific synopsis to comment on how cellular senescence can promote neurodegenerative diseases and to describe suitable targets for eliminating cellular senescence.

我们最近回顾了阐明细胞衰老对新冠肺炎并发症影响的科学文献[1]。最近的研究讨论了新冠肺炎患者细胞衰老与神经退行性疾病的关系[2-5]。因此，在本研究中，我们扩展了这一科学概要，以评论细胞衰老如何促进神经退行性疾病，并描述消除细胞衰老的合适靶点。

引用次数: 1

The Spread of Spectrin in Ataxia and Neurodegenerative Disease 精蛋白在共济失调和神经退行性疾病中的传播

Journal of experimental neurology

Pub Date : 2021-08-20 DOI: 10.33696/neurol.2.045

J. Morrow, Michael C. Stankewich

Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies. Most recognized are ataxias caused by missense, deletions, or truncations in the SPTBN2 gene that encodes beta III spectrin. Such mutations disrupt the organization of post-synaptic receptors, their active transport through the secretory pathway, and the organization and dynamics of the actin-based neuronal skeleton. Similar mutations in SPTAN1 that encodes alpha II spectrin cause severe and usually lethal neurodevelopmental defects including one form of early infantile epileptic encephalopathy type 5 (West syndrome). Defects in these and other spectrins are implicated in degenerative and psychiatric conditions. In recent published work, we describe in mice a novel variant of alpha II spectrin that results in a progressive ataxia with widespread neurodegenerative change. The action of this variant is distinct, in that rather than disrupting a constitutive ligand-binding function of spectrin, the mutation alters its response to calcium and calmodulin-regulated signaling pathways including its response to calpain activation. As such, it represents a novel spectrinopathy that targets a key regulatory pathway where calcium and tyrosine kinase signals converge. Here we briefly discuss the various roles of spectrin in neuronal processes and calcium activated regulatory inputs that control its participation in neuronal growth, organization, and remodeling. We hypothesize that damage to the neuronal spectrin scaffold may be a common final pathway in many neurodegenerative disorders. Targeting the pathways that regulate spectrin function may thus offer novel avenues for therapeutic intervention.

spectrin基因家族普遍存在的支架蛋白的实验性和遗传性缺陷导致了一系列的神经病理学。大多数公认的共济失调是由编码β-III血影蛋白的SPTBN2基因的错义、缺失或截短引起的。这种突变破坏了突触后受体的组织、它们通过分泌途径的主动转运，以及基于肌动蛋白的神经元骨架的组织和动力学。编码α-Ⅱspectrin的SPTAN1的类似突变会导致严重且通常致命的神经发育缺陷，包括一种形式的5型早期婴儿癫痫性脑病（West综合征）。这些和其他幽灵蛋白的缺陷与退行性疾病和精神疾病有关。在最近发表的工作中，我们在小鼠中描述了一种新的α-Ⅱspectrin变体，该变体导致进行性共济失调和广泛的神经退行性变化。这种变体的作用是不同的，因为突变并没有破坏spectrin的组成性配体结合功能，而是改变了其对钙和钙调素调节的信号通路的反应，包括对钙蛋白酶激活的反应。因此，它代表了一种新的光谱病，其靶向钙和酪氨酸激酶信号汇聚的关键调控途径。在这里，我们简要讨论了spectrin在神经元过程中的各种作用，以及控制其参与神经元生长、组织和重塑的钙激活调节输入。我们假设，对神经元spectrin支架的损伤可能是许多神经退行性疾病中常见的最终途径。因此，靶向调节spectrin功能的途径可能为治疗干预提供新的途径。

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引用次数: 5

Neural Population Computing: Parallel Distributed Processing, the Basal Ganglia, and Evolution 神经群体计算：并行分布式处理、基本Ganglia和进化

Journal of experimental neurology

Pub Date : 2021-06-30 DOI: 10.33696/neurol.2.038

S. Nadeau

It has been known for some time that representations in the central nervous system (CNS) are population encoded, that is, encoded as patterns of activity involving very large numbers of highly interconnected neurons in one or more neural networks extending over large expanses of the brain [1-11]. Nonetheless, understanding the computational processes occurring in pools of cortical neurons and the subcortical nuclei with which they interact continues to be one of the major challenges facing systems neuroscience.

一段时间以来，人们已经知道中枢神经系统(CNS)中的表征是群体编码的，也就是说，编码为涉及一个或多个神经网络中大量高度互联的神经元的活动模式，这些神经网络延伸到大脑的大片区域[1-11]。尽管如此，理解发生在皮质神经元池和与其相互作用的皮质下核中的计算过程仍然是系统神经科学面临的主要挑战之一。

引用次数: 0

Investigation of B2-AR, TLR2, PICALM, and BDNF Gene Variants in Iranian Alzheimer’s Patients and Their Response to Rivastigmine 伊朗阿尔茨海默病患者B2-AR、TLR2、PICALM和BDNF基因变异及其对利匹的明反应的研究

Journal of experimental neurology

Pub Date : 2021-06-30 DOI: 10.33696/neurol.2.041

Parvin Mohabattalab, F. R. Rad, H. Zamani, Fariba Shirvani, M. Zamani

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder with polygenic and multifactorial inheritance, determined by progressive loss of memory and other cognitive functions. AD is characterized by hallmark pathological changes such as extracellular aggregation of amyloid β (Aβ), intraneuronal neurofibrillary tangles that lead to brain atrophy and loss of neural tissue [1,2]. Alzheimer’s disease is categorized according to the age of onset as early-onset (EOAD) or lateonset AD (LOAD) [3]. And, based on family history, it is classified as sporadic (SAD) or familial Alzheimer’s disease (FAD) [4]. There are various genetic and environmental factors involved in the pathogenesis of AD which makes the etiology of the disease complicated however, testing for Abstract

阿尔茨海默病(AD)是一种毁灭性的神经退行性疾病，具有多基因和多因子遗传，由记忆力和其他认知功能的逐渐丧失决定。阿尔茨海默病的特征是细胞外淀粉样蛋白聚集(Aβ)、神经元内神经原纤维缠结等标志性病理改变，导致脑萎缩和神经组织丧失[1,2]。阿尔茨海默病根据发病年龄分为早发性AD (EOAD)和晚发性AD (LOAD)[3]。而且，根据家族史，它被分类为散发性(SAD)或家族性阿尔茨海默病(FAD)[4]。阿尔茨海默病的发病机制涉及多种遗传和环境因素，使得该病的病因复杂，检测方法摘要

引用次数: 0

Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine. 活动性厌食症的脆弱性和恢复力以及多巴胺的作用。

Journal of experimental neurology

Pub Date : 2021-03-01

Jeff A Beeler, Nesha S Burghardt

Activity-based anorexia (ABA) is a commonly used rodent model of anorexia nervosa that is based on observations made in rats decades ago. In recently published work, we describe using this paradigm to model vulnerability and resilience to anorexia nervosa in mice, where vulnerability is characterized by hyperactivity and life-threatening weight loss and resilience is characterized by adaptation and weight stabilization. Using genetically modified hyperdopaminergic mice, we also demonstrate that increased dopamine augments vulnerability to ABA. Here, we briefly review our findings and discuss how obtaining vulnerable and resilient phenotypes enhances utility of the ABA model for understanding the neurobiological basis of anorexia nervosa. We comment on our dopamine findings and close by discussing implications for clinical treatment.

活动性厌食症(ABA)是一种常用的啮齿动物神经性厌食症模型，它是基于几十年前对大鼠的观察而建立的。在最近发表的工作中，我们描述了使用这种范式来模拟小鼠对神经性厌食症的脆弱性和恢复力，其中脆弱性的特征是多动和危及生命的体重减轻，而恢复力的特征是适应和体重稳定。使用转基因高多巴胺能小鼠，我们也证明了多巴胺的增加增加了对ABA的易感性。在这里，我们简要回顾了我们的研究结果，并讨论了如何获得脆弱和弹性表型增强ABA模型的效用，以了解神经性厌食症的神经生物学基础。我们对多巴胺的发现进行评论，并讨论临床治疗的意义。

引用次数: 0

Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke. 评论:使用BACTRAC蛋白质组学数据库-缺血性卒中尿调蛋白表达。

Journal of experimental neurology

Pub Date : 2021-03-01

Gabriella-Salome K Armstrong, Jacqueline A Frank, Christopher J McLouth, Ann Stowe, Jill M Roberts, Amanda L Trout, Justin F Fraser, Keith Pennypacker

Introduction: Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle's loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI>25) and its relationship to stroke in patients.

Methods: Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent to Olink (Boston, MA) to determine proteomic expression via proximity extension assay. Uromodulin expression was recorded and analyzed using two tailed T-tests and linear regressions.

Results: The relationship between systemic and intracranial uromodulin, age, high BMI and hypertension were assessed. Systemic and intracranial uromodulin decreased with age (p<0.0001 and r²=0.343, p=0.0416 and r²=0.102) respectively. Systemic uromodulin expression increased with BMI>25 (p=0.014). Presence of hypertension decreased uromodulin's expression systemically (p=0.018) and intracranially (p=0.007).

Conclusions: Uromodulin was increased significantly in overweight patients, decreased significantly in older patients, and decreased in patients with hypertension. The increase in uromodulin in people with high BMI could be a protective reaction of the kidney to worsening conditions that make ischemic stroke more likely, with a goal of delaying dangerous outcomes. The decreased expression of uromodulin in older adults could be associated with the decline of general kidney function that accompanies aging. Hypertension can contribute to an AKI by decreasing perfusion to the kidney, therefore decreasing kidney function and uromodulin production. Further analyses are needed to understand the role of uromodulin following ischemic stroke.

尿调素(UMOD)是肾Henle’s袢厚升肢上皮细胞表达的一种糖蛋白。研究表明，尿调蛋白表达增加可能与成人心血管疾病风险降低有关。利用血液和血栓切除登记与协作(BACTRAC) (clinicaltrials.gov NCT03153683)，一个持续招募的组织库，我们旨在研究血清尿调素、年龄和高BMI (BMI>25)之间的关系及其与卒中的关系。方法:在取栓过程中，使用BACTRAC协议收集血栓远端和近端动脉血，并将其发送给Olink (Boston, MA)，通过邻近延伸法测定蛋白质组学表达。用双尾t检验和线性回归分析尿调素的表达。结果:评估全身和颅内尿调素与年龄、高BMI和高血压的关系。全身和颅内尿调素随年龄的增长而降低(p2=0.343, p=0.0416, r2=0.102)。BMI>25时，全身尿调素表达增加(p=0.014)。高血压降低尿调素的全身表达(p=0.018)和颅内表达(p=0.007)。结论:尿调素在超重患者中显著升高，在老年患者中显著降低，在高血压患者中显著降低。高BMI人群尿调蛋白的增加可能是肾脏对更容易发生缺血性中风的恶化情况的一种保护性反应，目的是延迟危险的结果。老年人尿调蛋白表达的降低可能与伴随衰老的一般肾功能下降有关。高血压可通过减少肾脏灌注，从而降低肾功能和尿调素的产生而导致AKI。需要进一步分析了解尿调蛋白在缺血性脑卒中中的作用。

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引用次数: 0

Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke 评论:使用BACTRAC蛋白质组学数据库-缺血性卒中尿调蛋白表达

Journal of experimental neurology

Pub Date : 2021-02-27 DOI: 10.33696/NEUROL.2.032

Gabriella-Salome K. Armstrong, J. Frank, C. McLouth, A. Stowe, Jill M Roberts, A. Trout, J. Fraser, K. Pennypacker

Introduction: Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle’s loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults. Utilizing the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683), a continuously enrolling tissue bank, we aimed to examine the associations between serum uromodulin, age, and high BMI (BMI>25) and its relationship to stroke in patients. Methods: Arterial blood distal and proximal to the thrombus was collected during a thrombectomy procedure using the BACTRAC protocol and sent to Olink (Boston, MA) to determine proteomic expression via proximity extension assay. Uromodulin expression was recorded and analyzed using two tailed T-tests and linear regressions. Results: The relationship between systemic and intracranial uromodulin, age, high BMI and hypertension were assessed. Systemic and intracranial uromodulin decreased with age (p<0.0001 and r2=0.343, p=0.0416 and r2=0.102) respectively. Systemic uromodulin expression increased with BMI>25 (p=0.014). Presence of hypertension decreased uromodulin’s expression systemically (p=0.018) and intracranially (p=0.007). Conclusions: Uromodulin was increased significantly in overweight patients, decreased significantly in older patients, and decreased in patients with hypertension. The increase in uromodulin in people with high BMI could be a protective reaction of the kidney to worsening conditions that make ischemic stroke more likely, with a goal of delaying dangerous outcomes. The decreased expression of uromodulin in older adults could be associated with the decline of general kidney function that accompanies aging. Hypertension can contribute to an AKI by decreasing perfusion to the kidney, therefore decreasing kidney function and uromodulin production. Further analyses are needed to understand the role of uromodulin following ischemic stroke.

引言：尿调素（UMOD）是一种糖蛋白，由肾脏中Henle’s环厚升肢上皮细胞表达。研究表明，尿调素表达增加可能与成年人患心血管疾病的风险降低有关。利用血液和凝块血栓切除术注册与协作（BACTRAC）（clinicaltrials.gov NCT03153683），一个持续注册的组织库，我们旨在检查患者血清尿调素、年龄和高BMI（BMI>25）之间的关系及其与中风的关系。方法：在血栓切除术中，使用BACTRAC方案收集血栓远端和近端的动脉血，并将其送往Olink（马萨诸塞州波士顿），通过邻近延伸分析测定蛋白质组学表达。使用双尾T检验和线性回归来记录和分析尿调素的表达。结果：评估了全身和颅内尿调素、年龄、高BMI和高血压之间的关系。全身和颅内尿调素随着年龄的增长而降低（p25（p=0.014）。高血压的存在降低了尿调素在全身和颅内的表达（p=0.018）。结论：超重患者尿调素显著增加，老年患者尿调蛋白显著降低，高血压患者尿调元降低。高BMI人群尿调素的增加可能是肾脏对更可能发生缺血性中风的恶化状况的保护性反应，目的是延缓危险的结果。老年人尿调素表达的减少可能与伴随衰老的一般肾功能下降有关。高血压可通过减少对肾脏的灌注，从而降低肾功能和尿调素的产生，从而导致AKI。需要进一步的分析来了解缺血性中风后尿调素的作用。

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引用次数: 2

Commentary on Vulnerability and Resilience to Activity-Based Anorexia and the Role of Dopamine 活动性厌食症的脆弱性和恢复力以及多巴胺的作用

Journal of experimental neurology

Pub Date : 2021-02-25 DOI: 10.33696/NEUROL.2.031

J. Beeler, N. Burghardt

Activity-based anorexia (ABA) is a commonly used rodent model of anorexia nervosa that is based on observations made in rats decades ago. In recently published work, we describe using this paradigm to model vulnerability and resilience to anorexia nervosa in mice, where vulnerability is characterized by hyperactivity and life-threatening weight loss and resilience is characterized by adaptation and weight stabilization. Using genetically modified hyperdopaminergic mice, we also demonstrate that increased dopamine augments vulnerability to ABA. Here, we briefly review our findings and discuss how obtaining vulnerable and resilient phenotypes enhances utility of the ABA model for understanding the neurobiological basis of anorexia nervosa. We comment on our dopamine findings and close by discussing implications for clinical treatment.

活动性厌食症（ABA）是一种常用的神经性厌食症啮齿类动物模型，基于几十年前对大鼠的观察。在最近发表的工作中，我们描述了使用这种范式来模拟小鼠对神经性厌食症的脆弱性和恢复力，其中脆弱性以多动和危及生命的体重减轻为特征，而恢复力以适应和体重稳定为特征。使用转基因的高多巴胺能小鼠，我们还证明多巴胺的增加增加了对ABA的易感性。在这里，我们简要回顾了我们的发现，并讨论了获得脆弱和有弹性的表型如何提高ABA模型在理解神经性厌食症的神经生物学基础方面的效用。我们评论了我们的多巴胺研究结果，最后讨论了对临床治疗的影响。

引用次数: 3

Retroviral Elements in Human Evolution and Neural Development 逆转录病毒在人类进化和神经发育中的作用

Journal of experimental neurology

Pub Date : 2021-02-22 DOI: 10.33696/NEUROL.2.028

Tongguang Wang, Tara T. Doucet-O’Hare, L. Henderson, Rachel P. M. Abrams, A. Nath

Human embryogenesis and the development of its most unique product, the human brain, are believed to be precisely regulated by factors adopted during human evolution that differentiate us from other species. Nevertheless, increasing evidence shows an unthinkable “alien” factor may have contributed to the process. Pervasive horizontal gene transfer between species mediated by retroviruses is such a defining factor of evolution [1]. Retroviral infections occurred in germline cells and were able to transfer the genomic codes vertically from parent to offspring. These genes once integrated into the host chromosome, can get dispersed and exist in multiple mutated copies throughout the host genome. As a result, retroviral genes and other retro elements contribute to about 50% of the human genome. Of these, 20% belong to the group of LINEs and over 8% consists of HERVs which are relatively intact since they were acquired more recently [2]. From an evolutionary point of view, these retroviral elements have at least a few known functions that could benefit the human host. Generally, the vast amount of such “relic” genes in the genome can provide a specific buffer zone to preserve functional genes against further viral infections and other gene mutation causing events. The similarities of gene sequences and functions provide a more specific competition to limit further similar viral infections [3]. These functions are evidenced by the abnormal shares of mutations and translocations within the retroviral elements compared with other functional genes. Other functions of the HERV proteins lent to the host include the immune regulatory functions, such as an immunosuppressive function mediated by a domain located in the transmembrane subunit of the HERV-W [4,5]. In the present review, we focus on the effects of retroviral elements on human embryogenesis and neural development.

人类胚胎发生及其最独特产物人脑的发育被认为是由人类进化过程中所采用的因素精确调节的，这些因素使我们与其他物种区别开来。然而，越来越多的证据表明，一种不可想象的“外来”因素可能促成了这一过程。由逆转录病毒介导的物种间普遍的水平基因转移是进化的一个决定性因素。逆转录病毒感染发生在生殖细胞中，并且能够将基因组密码垂直地从亲代传递给后代。这些基因一旦整合到宿主染色体上，就会分散，并在宿主基因组中以多个突变副本的形式存在。因此，逆转录病毒基因和其他逆转录因子占人类基因组的50%左右。其中，20%属于line组，超过8%由herv组成，这些herv相对完整，因为它们是最近获得的。从进化的角度来看，这些逆转录病毒至少有一些已知的功能对人类宿主有益。一般来说，基因组中大量这样的“遗物”基因可以提供一个特定的缓冲区，以保护功能基因免受进一步的病毒感染和其他基因突变引起的事件。基因序列和功能的相似性为限制进一步的类似病毒感染提供了更具体的竞争。与其他功能基因相比，逆转录病毒元件中突变和易位的异常份额证明了这些功能。借给宿主的HERV蛋白的其他功能包括免疫调节功能，例如由HERV- w跨膜亚基中的一个结构域介导的免疫抑制功能[4,5]。本文就逆转录病毒因子在人类胚胎发生和神经发育中的作用作一综述。

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引用次数: 2

Cathepsin D: A Candidate Link between Amyloid β-protein and Tauopathy in Alzheimer Disease 组织蛋白酶D:淀粉样蛋白β-蛋白与阿尔茨海默病tau病变之间的候选联系

Journal of experimental neurology

Pub Date : 2021-02-04 DOI: 10.33696/NEUROL.2.029

Caitlin N Suire, M. Leissring

Alzheimer disease (AD) is a debilitating neurodegenerative disorder characterized by extracellular deposition of the amyloid β-protein (Aβ) and intraneuronal accumulation of the microtubule-associated protein, tau. Despite a wealth of experimental and genetic evidence implicating both Aβ and tau in the pathogenesis of AD, the precise molecular links between these two pathological hallmarks have remained surprisingly elusive. Here, we review emerging evidence for a critical nexus among Aβ, tau, and the lysosomal protease cathepsin D (CatD) that we hypothesize may play a pivotal role in the etiology of AD. CatD degrades both Aβ and tau in vitro, but the in vivo relevance of this lysosomal protease to these principally extracellular and cytosolic proteins, respectively, had remained undefined for many decades. Recently, however, our group found that genetic deletion of CatD in mice results in dramatic accumulation of Aβ in lysosomes, revealing that Aβ is normally trafficked to lysosomes in substantial quantities. Moreover, emerging evidence suggests that tau is also trafficked to the lysosome via chaperone-mediated autophagy and other trafficking pathways. Thus, Aβ, tau and CatD are colocalized in the lysosome, an organelle that shows dysfunction early in AD pathogenesis, where they can potentially interact. Notably, we discovered that Aβ42—the Aβ species most strongly linked to AD pathogenesis—is a highly potent, low-nanomolar, competitive inhibitor of CatD. Taking these observations together, we hypothesize that Aβ42 may trigger tauopathy by competitive inhibition of CatD-mediated degradation of tau—pathogenic forms of tau, in particular. Herein, we review the evidence supporting this hypothesis and explore the implications for the molecular pathogenesis of AD. Future research into these novel mechanistic links among Aβ, tau and CatD promises to expand our understanding of the etiology of AD and could potentially lead to novel therapeutic approaches for combatting this devastating disease of brain and mind.

阿尔茨海默病（AD）是一种使人衰弱的神经退行性疾病，其特征是淀粉样β蛋白（aβ）的细胞外沉积和微管相关蛋白tau的神经内积聚。尽管有大量的实验和遗传学证据表明aβ和tau都参与了AD的发病机制，但这两种病理特征之间的确切分子联系仍然令人惊讶地难以捉摸。在这里，我们回顾了aβ、tau和溶酶体蛋白酶组织蛋白酶D（CatD）之间存在关键联系的新证据，我们假设它们可能在AD的病因中发挥关键作用。CatD在体外降解aβ和tau，但这种溶酶体蛋白酶分别与这些主要的细胞外和胞质蛋白的体内相关性几十年来一直不明确。然而，最近，我们的研究小组发现，小鼠CatD的基因缺失会导致Aβ在溶酶体中的大量积累，这表明Aβ通常会大量输送到溶酶体。此外，新出现的证据表明，tau也通过伴侣介导的自噬和其他运输途径运输到溶酶体。因此，Aβ、tau和CatD在溶酶体中共定位，溶酶体是AD发病早期表现出功能障碍的细胞器，它们可能在溶酶体中相互作用。值得注意的是，我们发现Aβ42——与AD发病机制密切相关的Aβ物种——是一种高效、低纳摩尔、竞争性的CatD抑制剂。综合这些观察结果，我们假设Aβ42可能通过竞争性抑制CatD介导的tau降解而引发tau病，尤其是tau的致病形式。在此，我们回顾了支持这一假设的证据，并探讨了对AD分子发病机制的影响。未来对Aβ、tau和CatD之间这些新的机制联系的研究有望扩大我们对AD病因的理解，并可能为对抗这种毁灭性的脑和精神疾病带来新的治疗方法。

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引用次数: 11