BDNF

03月27日的《热心肠日报》，我们解读了 15 篇文献，关注：菌群-肠-脑轴，成瘾，抑郁，儿童，神经行为发育，脑容量，认知功能，眼病，益生菌，方法学，安斯泰来，艾伯维，Landos Biopharma，石药集团，康宁杰瑞，GNC，Novonesis。 ​​ 该篇日报由R·AI辅助创作生成，人工审核校对。 Nature Outlook：肠道微生物与酒精成瘾的关系 Nature——[64.8] ① 近年来的研究开始揭示肠道微生物组与成瘾行为之间的联系，指出肠道微生物失衡可能会促使大脑产生促进成瘾的信号；② 有研究者认为，肠道中的较高水平的白色念珠菌可能会导致小鼠增加酒精成瘾，这为治疗酒精使用障碍（AUD）提供了新的治疗靶点；③ 肠道与大脑之间的复杂通信被认为通过2种主要方式影响与成瘾相关的行为：“肠道渗漏”引起的炎症反应和肠道微生物产生的神经活性分子（如GABA、5-羟色胺、多巴胺、短链脂肪酸）均可对大脑功能产生影响；④ 早期的肠道微生物群失衡可能使个体更容易成瘾，研究发现肠道微生物组的改变与成瘾行为的脑回路有相关；⑤ 尽管目前对于针对肠道微生物组的治疗方法仍需进一步研究，但营养干预、益生菌和益生元等方法可能最终提高治疗AUD成功的几率。 【原文信息】 Could the gut give rise to alcohol addiction? 2024-03-07 , doi: 10.1038/d41586-024-00667-8 国内团队：肠道菌群失调促进抑郁的神经免疫新机制 Microbiome——[15.5] ① 北京中医药大学陈家旭、暨南大学黄俊卿以及李晓娟作为共同通讯作者发表研究，发现慢性不可预测的轻度压力（CUMS）会诱导小鼠展现出明显的抑郁症样行为和认知障碍，这与肠道菌群显著失调、脂多糖（LPS）水平升高有关；② 外周和中枢的补体C3激活以及中枢C3/CR3介导的异常突触修剪在小脑胶质细胞中也被观察到；③ 将CUMS诱导的抑郁模型小鼠的肠菌移植到受体小鼠，会诱发其出现类似抑郁行为和伴随的认知功能障碍，前额叶皮质中补体C3/CR3途径的活化增加，小脑胶质细胞介导的突触修剪异常；④ 抗抑郁药物和来自抗抑郁药物处理的供体的菌群移植能改善抑郁症样行为，恢复肠道菌群失调，并抑制异常的突触剪裁。 【原文信息】 Gut dysbiosis induces the development of depression-like behavior through abnormal synapse pruning in microglia-mediated by complement C3 2024-02-20 , doi: 10.1186/s40168-024-01756-6 儿童肠道菌群与行为表现的集群特异性关联研究 Microbiome——[15.5] ① 本研究揭示了肠道菌群与学龄前儿童行为结果之间的集群特异性关联，为个性化干预提供了新的思路；② 通过对248名典型发育儿童的肠道菌群组成进行分类，发现四种不同的肠道菌群聚类，其中富含拟杆菌和双歧杆菌（Ba2）的菌群聚类具有最独特的粪便代谢组；③ 高双歧杆菌丰度（Bif）及Ba2聚类与较低的适应技能分数及其社交技能子成分相关；④ Ba2聚类的粪便组氨酸向尿刊酸转化率显著降低，这与社交技能分数低下有关；⑤ Ba2聚类中参与半乳糖代谢的化合物（如水苏糖、棉子糖、α-D-葡萄糖）水平增加，其中α-D-葡萄糖与日常生活技能分数（即执行基本日常任务的能力）呈集群依赖性关联。 【原文信息】 Cluster-specific associations between the gut microbiota and behavioral outcomes in preschool-aged children 2024-03-21 , doi: 10.1186/s40168-024-01773-5 胎儿PFAS暴露、肠道菌群失调与儿童神经行为发育 Journal of Hazardous Materials——[13.6] ① 本研究揭示了孕期全氟烷基物质（PFAS）暴露、肠道菌群失衡与儿童神经行为发展之间的关联，强调了肠道菌群在PFAS神经毒性中的重要作用；② 暴露于全氟己烷磺酸（PFHxS）的儿童表现出更多的行为和外化问题，且其肠道菌群的多样性改变；③ PFHxS浓度与肠道中肠球菌属的相对丰度增加有关，而与多种短链脂肪酸产生菌属如高氏瘤胃球菌的相对丰度降低有关；④ PFHxS暴露还与氧化磷酸化增加有关；⑤ 肠道菌群α和β多样性与行为问题和外显问题显著相关，且增加的α多样性在PFHxS暴露与行为问题的关联中发挥了调节作用；⑥ 高氏瘤胃球菌的丰度与亲社会行为得分呈正相关。 【原文信息】 Prenatal PFAS exposure, gut microbiota dysbiosis, and neurobehavioral development in childhood 2024-03-03 , doi: 10.1016/j.jhazmat.2024.133920 西安交大：肠道菌群、脑容量和智力间有何因果关系？ Biological Psychiatry——[10.6] ① 西安交通大学杨铁林和郭燕与团队使用来自肠道菌群（n=18340）和智力（n=269867）最大规模的基因组关联研究进行双样本孟德尔随机化（MR）分析，澄清肠道菌群与智力间的因果关系；② 草酸杆菌属对智力有风险影响，而梭形杆菌属对智力具有保护作用；③ 两步MR分析显示，梭形杆菌属对智力的影响部分通过调节大脑体积来介导，介导比例为33.6%；④ 这些发现可能有助于重新理解肠-脑轴的作用，并为预防认知障碍开发新的干预方法提供线索。 【原文信息】 The causal relationship between gut microbiota, brain volume, and intelligence: a two-step Mendelian randomization analysis 2024-03-01 , doi: 10.1016/j.biopsych.2024.02.1012 产脂多糖的肠菌会引发小鼠认知障碍？ Brain Behavior and Immunity——[15.1] ① 探究了肠道菌群弗格森埃希菌（NK2001）、Veillonella infantium（NK2002）和屎肠球菌（NK2003）对小鼠认知障碍样行为、神经炎症和结肠炎的影响；② NK2001和NK2002通过产生LPS，而NK2003即使不产生LPS也能通过肠-血液/迷走神经-脑和肠-血液-脑途径转移如肽聚糖等副产物到脑部，引发认知障碍；③ 这些肠菌会增加小鼠海马区TNF-α表达、Iba1阳性细胞群的大小，并降低脑源性神经营养因子（BDNF）的表达；④ 迷走神经切除会显著降低NK2001或NK2002引起的认知障碍行为、海马区Iba1阳性细胞群和TNF-α表达，并增加NK2001或NK2002抑制的海马区BDNF表达。 【原文信息】 Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice 2024-02-28 , doi: 10.1016/j.bbi.2024.02.031 肠道菌群如何影响眼表稳态和相关疾病？（综述） Progress in Retinal and Eye Research——[17.8] ① 越来越多的证据表明肠道微生物群与眼部表面疾病间有关联，肠道菌群的变化可能会影响眼表稳态的维持，进而影响眼表疾病的发生或持续；② 干眼症是与肠道菌群变化关系最为明确的眼表疾病；③ 通过解析肠道菌群对眼表稳态的影响，可以开发针对眼表疾病的创新治疗方法，如使用益生元和/或益生菌，但仍需进一步研究；④ 优化肠道菌群稳态是整体治疗方法的一部分，考虑到眼表受神经、激素和免疫因素的调节。 【原文信息】 How gut microbiota may impact ocular surface homeostasis and related disorders 2024-03-07 , doi: 10.1016/j.preteyeres.2024.101250 江南大学：挑选出治疗抑郁焦虑的益生菌最佳组合 Psychological Medicine——[6.9] ① 江南大学的杨超团队发表文章，通过网络荟萃分析评估了不同益生菌组合对抑郁、焦虑和压力症状的改善效果，发现乳杆菌、双歧杆菌以及两者的联用在治疗焦虑和抑郁方面具有显著效果；② 纳入45项符合条件的试验，涉及4053名参与者和10种干预措施，证据质量评定为高或中等；③ 双歧杆菌在改善焦虑症状方面的效果最佳（标准化均数差SMD = -0.80），其次是乳杆菌（SMD = -0.49）；④ 对于多菌株联用，与其他干预措施相比，乳杆菌+双歧杆菌的组合对抑郁有积极影响（SMD = -0.41）。 【原文信息】 Assessment of optimal combinations of therapeutic probiotics for depression, anxiety, and stress 2024-03-18 , doi: 10.1017/S0033291724000679 Nature子刊：脑-肠-菌群轴中的微生物组数据分析-概念与基础（观点第1部分） Nature Mental Health——[0] ① 脑-肠-菌群轴指肠道微生物对情绪和行为的影响，相关的研究和分析一直在进步但仍然很复杂，Nature mental health发表了观点性文章，分为1、2两部分，旨在对该领域的微生物组数据的分析和解读进行总结；② 介绍在分析数据之前所要考虑的基本因素以及α、β多样性、核心菌群、差异特征丰度以及功能推理的分析方法，同时提供了一个带有注释的R语言分析示例；③ 该观点文章提出在微生物组研究中，明确区分探索性分析和验证性假设检验非常重要，而清晰沟通和可重复的方法是解释微生物组研究中混杂因素的关键；④ 线性建模包括将混杂因子作为统计模型中的协变量是处理微生物组研究中混杂因子的常用策略；⑤ Wet-Lab协议，包括测序协议，极大地影响微生物组测序数据的质量和内容。 【原文信息】 Bugs as features (part 1): concepts and foundations for the compositional data analysis of the microbiome–gut–brain axis 2023-12-05 , doi: 10.1038/s44220-023-00148-3 Nature子刊：脑-肠-菌群轴中的微生物组数据分析-概念与基础（观点第2部分） Nature Mental Health——[0] ① 脑-肠-菌群轴研究涉及多学科多领域，如微生物学、生态学、精神病学、计算生物学和流行病学等，本部分的内容介绍相关的技术和知识，旨在回答“如何建立因果关系？”，“如何整合多组学技术”以及“如何研究宿主-菌群互作的动态平衡”等问题；② 因果关系：线性的因果关系-格兰杰因果关系，通常指由A的数据，可以预测B的性状，但微生物组与脑肠轴的关系更为复杂，可以通过因果推理分析、中介分析或孟德尔随机化来进行分析；③ 高维数据科学：脑-肠-菌群轴研究通常涉及到高维数据，可以通过对样本进行分层和聚类以及多组学整合来进行分析；④ 探索mesoscale-中尺度特征：中尺度是理论生态学中的重要概念（既不关注最小部分也不关注全部），可以用来更好的解释和鉴别群落水平的模式特征；⑤ 时变信号：微生物组是不断变化的动态生态系统，需一事一例地考虑时间序列分析。 【原文信息】 Bugs as features (part 2): a perspective on enriching microbiome–gut–brain axis analyses 2023-12-05 , doi: 10.1038/s44220-023-00149-2 安斯泰来C LDN18.2单抗药在日本获批，一线治疗胃癌 ① 3月26日，安斯泰来宣布，VYLOY（zolbetuximab）获得日本厚生劳动省批准，用于治疗Claudin18.2（CLDN18.2）阳性、不可切除、晚期或复发性胃癌患者；② VYLOY成为全球首个也是目前唯一一个获得全球监管机构批准的CLDN18.2靶向疗法；③ 此次批准基于3期研究SPOTLIGHT和GLOW试验结果；④ 研究结果显示，VYLOY与化疗联合使用，能够显著改善患者的无进展生存期（PFS）和总生存期（OS）；⑤ 目前，安斯泰来已经向全球多个监管机构提交了VYLOY的上市申请，正处于审查阶段。 【原文信息】 Astellas’ VYLOY™ (zolbetuximab) Approved in Japan for Treatment of Gastric Cancer 2024-03-26 , astellas 艾伯维超2亿美元收购Landos Biopharma ① 3月26日，艾伯维宣布将以超2亿美元（约合人民币14.4亿元）的价格收购Landos Biopharma公司；② Landos的主打项目NX-13是一款潜在“同类最快”的口服NLRX1激动剂，用于治疗溃疡性结肠炎，目前处于2期临床阶段；③ NX-13通过减少活性氧和氧化应激，同时减少促炎信号，发挥抗炎作用并促进肠上皮修复；④ 双方交易包括1.375亿美元的预付款和7500万美元的里程碑付款，预计交易将于2024年第二季度完成。 【原文信息】 艾伯维达成超2亿美元收购，囊获潜在“first-in-class”小分子！ 2024-03-26 , 药明康德 石药集团司美格鲁肽获批开展减肥临床试验 ① 3月25日，石药集团宣布，其开发的司美格鲁肽注射液获国家药监局批准，在中国开展成人超重或肥胖患者体重管理的临床试验；② 这是该产品继成人2型糖尿病患者的血糖控制后，获批临床试验的第二个适应证；③ 石药集团的司美格鲁肽产品采用化学合成法制备，纯度高，杂质水平低，与DNA重组技术制备的产品相比具有更好的安全性和稳定性；④ 该产品是全球首个获批的化学合成的司美格鲁肽产品，目前属于中国化药注册分类2.2类。 【原文信息】 石药集团司美格鲁肽获批开展减肥临床试验 2024-03-25 , 医药魔方info 康宁杰瑞实体瘤新药JSKN033澳大利亚完成首例患者给药 ① 3月26日，康宁杰瑞宣布，JSKN033治疗HER2表达、晚期或转移性实体瘤的临床研究JSKN033-101，已经在澳大利亚完成首例患者给药；② JSKN033是一种皮下注射HER2双抗ADC与PD-L1复方制剂，旨在提高治疗效果并延长生存期；③ 该药物是全球首个皮下注射HER2双特异性抗体偶联药物和免疫检查点抑制剂复方制剂；④ JSKN033-101研究包括1/2期试验两部分，2期剂量扩展阶段将评估JSKN033在RP2D剂量下对HER2表达消化道肿瘤的疗效和安全性。 【原文信息】 康宁杰瑞皮下注射药物JSKN033在澳大利亚完成首例患者给药 2024-03-26 , 江苏康宁杰瑞生物制药有限公司 GNC健安喜与Novonesis诺和新元达成战略合作 ① 近日，美国膳食营养补充剂品牌GNC健安喜宣布，与Novonesis诺和新元达成深度战略合作；② 双方合作将在益生菌领域探索新空间，共同构建行业市场的新生态；③ 据报道，双方将于今年四月推出基于Novonesis的明星菌株Pylopass的全新益生菌产品，旨在为消费者提供更加优质、健康的营养食品。 【原文信息】 GNC健安喜携手Novonesis诺和新元达成战略合作 共绘益生菌市场新蓝图 2024-03-20 , 中华网 感谢本期日报的审核者：mildbreeze，九卿臣，圆圈儿，章台柳，好雨，617，Richard 点击阅读过去10天的日报： 0326 | 100分综述详解：IBD细胞因子疗法最前沿 0325 | 大肠癌患病为何年轻化？遗传与生活方式的双重影响 0324 | 大型临床试验：补钙补D如何影响老年女性长期健康？ 0323 | Lancet+JAMA领衔，聚焦炎症性肠病诊断与治疗 0322 | 陈豪燕/洪洁等Cell子刊：免疫治疗对老年人更有效，肠道菌群或是隐藏功臣 0321 | 今日Nature双发：促肠癌菌和宿主-菌群互作研究均有新突破 0320 | 12页高分综述解析：抗生素扰乱菌群，对宿主代谢有何影响？ 0319 | 今日Cell：国内团队发现新肠道激素，连起肠肝轴胆固醇代谢调控 0318 | NEJM双发：大肠癌无创检测取得新突破 0317 | Cell子刊：多组学+长追踪，深度解析人体菌群动态和与宿主的互作

本文为转化医学网原创，转载请注明出处 作者：Jerry 导读： 靶向失调的神经系统可能是癌症治疗的一种新策略。然而，肝内胆管癌(ICC)是否能够建立自己的神经网络，以及神经递质在ICC进展中的作用仍不得而知。 3月8日，复旦大学钦伦秀/董琼珠研究团队在期刊《Signal Transduction and Targeted Therapy》 上发表了题为“Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis”的研究论文，研究发现，CAMKII的小分子抑制剂KN93能显著抑制ICC细胞的迁移，增强对吉西他滨的敏感性。 乙酰胆碱/CHRNA5轴通过CAMKII/GSK3β信号通路增加β-catenin的表达，促进ICC转移和对吉西他滨的耐药，CAMKII抑制剂KN93可能是对抗ICC转移的有效治疗策略。 https://www.nature.com/articles/s41392-024-01761-z#Sec9 研究背景 01 肝内胆管癌(ICC)约占原发性肝脏恶性肿瘤的5-10%，其发病率在全球范围内呈上升趋势。ICC通常在晚期诊断出来，进行根治性切除的机会有限，由于缺乏有效的治疗选择，其预后非常糟糕。因此，有必要揭示ICC进展的分子机制，以开发新的治疗策略。 神经周围浸润(PNI)，定义为癌细胞出现在神经鞘的任何层或周围至少33%的神经纤维周长，在包括ICC在内的许多实体恶性肿瘤中都有报道。PNI曾被认为是癌细胞与神经关系的主要表现。最近的研究揭示了癌细胞与神经之间的串扰，癌细胞可以分泌神经生长因子(NGF)诱导神经的生长，而神经又可以释放效应分子调节肿瘤细胞的恶性表型。神经成瘾在癌症中的概念最近被提出，指的是神经系统与肿瘤发展之间的复杂关系，临床和临床前现象证明外周和中枢神经系统在控制肿瘤的形成和转移中都起着至关重要的作用。越来越多的证据表明，神经在肿瘤发生和癌症进展的调节中起着核心作用。 神经营养因子，如NGF、脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)，是参与神经元生长和PNI的蛋白质。在神经发育过程中，BDNF激活TrKB信号通路，促进神经的生长。在胰腺导管腺癌中，肿瘤细胞分泌BDNF诱导神经突生长，促进神经浸润在卵巢癌中，儿茶酚胺介导的ADRB3/cAMP/Epac/JNK信号通路的激活上调BDNF的表达，促进轴突发生。既往研究发现，BDNF在ICC中的表达明显高于邻近正常组织，且BDNF水平与PNI的发生呈正相关，提示BDNF可能在ICC中PNI的发生过程中发挥重要作用。 研究发现 02 鉴于CAMKII在调节β-catenin活性中发挥重要作用，而β-catenin是ICC化疗敏感性的关键调节因子，CAMKII活性可能与ICC的化疗反应密切相关。为了进一步探索CAMKII活性与ICC患者吉西他滨疗效之间的潜在相关性，研究人员收集了19例接受吉西他滨为基础化疗的ICC患者的样本。免疫组织化学染色显示对吉西他滨为基础的化疗耐药的ICC患者p-CAMKII表达水平较高，提示CAMKII可能作为ICC的治疗靶点。体外实验显示，CAMKII抑制剂KN93可增加吉西他滨的敏感性，KN93与吉西他滨具有协同抗肿瘤作用。进一步的体内实验也证实了KN93和吉西他滨联合治疗比单药治疗更有效，并且在接受不同治疗的小鼠中未观察到这些药物的明显毒性。此外，联合用药能更大程度地诱导细胞凋亡并抑制Ki67的表达。 综上，抑制CAMKII可抑制ICC的恶性表型并增加其对吉西他滨的敏感性，KN93联合吉西他滨可能是治疗ICC的一种新的治疗策略。 CAMKII抑制剂KN93与吉西他滨联合在ICC中表现出增强的抗肿瘤活性 研究结论 03 综上所述，神经和ICC细胞都能分泌乙酰胆碱，从而产生富含乙酰胆碱的肿瘤微环境。乙酰胆碱/CHRNA5轴介导的Ca2+流入激活CAMKII，其直接磷酸化和失活GSK3β，增加β-catenin的稳定性，促进ICC的恶性表型。 CAMKII抑制剂KN93不仅可以抑制ICC细胞的迁移能力，还可以增强其对吉西他滨的敏感性，提示KN93与吉西他滨联合治疗ICC可能是一种新的治疗策略，特别是在PNI患者中。 参考资料： https://www.nature.com/articles/s41392-024-01761-z#Sec9 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。 热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！ 点击对应文字 查看详情

STOCKHOLM, SWEDEN / ACCESSWIRE / March 7, 2024 / AlzeCure Pharma (STO:ALZCUR)(FRA:AC6) AlzeCure Pharma AB (publ) (FN STO: ALZCUR), a pharmaceutical company that develops small molecule drug candidates for CNS diseases, focusing on Alzheimer's disease and pain, today announced that the company's presentation at the Alzheimer's conference AD/PD 2024, regarding new preclinical data with its leading clinical drug candidate NeuroRestore ACD856, which is being developed with a focus on Alzheimer's disease, is now available on the company's website. The abstract, titled ACD856 is a biased positive allosteric modulator of Trk-receptors - Enhances neurite outgrowth but do not affect pain signaling , was presented by Pontus Forsell, Head of Discovery and Research at AlzeCure, and includes new preclinical data with the lead clinical drug candidate ACD856, which is part of the NeuroRestore platform. Data from the study show that ACD856 functions as a so-called biased PAM (positive allosteric modulator), i.e. that the substance potentiates certain signaling pathways but not others, which means that the substance can have potent effects and at the same time maintain a good safety profile. The results show that ACD856 can stimulate nerve cell growth, something that is important for communication between nerve cells. In addition, the substance improves memory and learning ability in preclinical models. In contrast, pain signaling is not affected, which indicates a selective stimulation of specific signaling pathways. ACD856 is a Trk-PAM and enhances BDNF and NGF signaling, which among other things play an important role in normal nerve cell function and maintaining brain health. The substance is under clinical development as a symptom-relieving treatment for disease states where the cognitive ability is impaired, for example in Alzheimer's disease. New preclinical data also suggest that ACD856 has potential protective and disease-modifying effects. "These new data with ACD856 show that the substance has growth-stimulating and memory-enhancing effects, without affecting pain signaling. This selective stimulatory effect bodes well for further clinical development," said Pontus Forsell. "With the positive clinical results we previously obtained with ACD856, as well as additional new preclinical results supporting a disease-modifying effect, we have a promising drug candidate in the Alzheimer's field, which is gratifying considering the very large medical need," said AlzeCure Pharma's CEO Martin Jönsson. The authors of the abstract are Pontus Forsell, Veronica Lidell, Azita Rasti, Gunnar Nordvall and Johan Sandin. The presentation is available on AlzeCure's website: ( ). For more information, please contact Martin Jönsson, CEO Tel: +46 707 86 94 43 martin.jonsson@alzecurepharma.com About AlzeCure Pharma AB (publ) AlzeCure® is a Swedish pharmaceutical company that develops new innovative drug therapies for the treatment of severe diseases and conditions that affect the central nervous system, such as Alzheimer's disease and pain - indications for which currently available treatment is very limited. The company is listed on Nasdaq First North Premier Growth Market and is developing several parallel drug candidates based on three research platforms: NeuroRestore®, Alzstatin® and Painless. NeuroRestore consists of two symptomatic drug candidates where the unique mechanism of action allows for multiple indications, including Alzheimer's disease, as well as cognitive disorders associated with traumatic brain injury, sleep apnea and Parkinson's disease, as well as for depression treatment. The Alzstatin platform focuses on developing disease-modifying and preventive drug candidates for early treatment of Alzheimer's disease and comprises two drug candidates. Painless is the company's research platform in the field of pain and contains two projects: ACD440, which is a drug candidate in the clinical development phase for the treatment of neuropathic pain, and TrkA-NAM, which targets severe pain in conditions such as osteoarthritis. AlzeCure aims to pursue its own projects through preclinical research and development through an early clinical phase, and is continually working on business development to find suitable outlicensing solutions, alternatively partnership, with other pharmaceutical companies. FNCA Sweden AB is the company's Certified Adviser. For more information, please visit . About NeuroRestore NeuroRestore is a platform of symptom-relieving drug candidates for disease states in which cognitive ability is impaired, e.g. Alzheimer's Disease, sleep apnea, traumatic brain injury and Parkinson's disease. NeuroRestore stimulates several important signaling pathways in the brain, which among other things leads to improved cognition. Preclinical studies with NeuroRestore have shown that AlzeCure's drug candidates enhance communication between the nerve cells and improve cognitive ability. The NeuroRestore substances are so called Trk-PAMs which stimulate specific signaling pathways in the central nervous system known as neurotrophins, the most well-known being NGF (Nerve Growth Factor) and BDNF (Brain Derived Neurotrophic Factor). The levels of NGF and BDNF are disturbed in several disease states and the signaling is reduced. The impaired function impairs communication between the synapses, i.e. the contact surfaces of the nerve endings, as well as reducing the possibility of survival for the nerve cells, which gives rise to the cognitive impairments. Neurotrophins play a crucial role for the function of nerve cells, and a disturbed function of BDNF has a strong genetic link to impaired cognitive ability in several different diseases, such as Alzheimer's, Parkinson's disease, traumatic brain injury and sleep disorders. There is also a link between BDNF signaling and depression, something that has been further strengthened in recent years. In addition to cognitive-enhancing effects, new preclinical data also show that NeuroRestore substances have a positive effect on mitochondrial function and cell survival, which could indicate potential disease-modifying effects. The leading drug candidate in the platform, ACD856, has recently completed clinical phase I studies and demonstrated positive effects there that support continued development of the program. About Alzheimer's disease Alzheimer's disease is the most common form of dementia, affecting approximately 55 million people worldwide. Alzheimer's disease is a lethal disorder that also has a large impact on both relatives and the society. Today, preventive and disease modifying treatments are missing. The main risk factors to develop Alzheimer's are age and genetic causes. Even though the disease can start as early as between 40 and 65 years of age, it is most common after 65 years. Significant investments in Alzheimer research are being made because of the significant unmet medical need and the large cost of this disease for healthcare and society. The total global costs for dementia related diseases is estimated to about $1,300 billion globally in 2019. Given the lack of both effective symptomatic treatments and disease modifying treatments, the need for new effective therapies is acute.The few approved drugs on the market today have only a limited symptomatic effect and can produce dose limiting side effects. A disease modifying treatment for Alzheimer's disease is estimated to reach more than $15 billion in annual sales. In Sweden, approximately 100,000 people suffer from Alzheimer's disease with a healthcare cost of about SEK 63 billion yearly, which is more than for cancer and cardiovascular diseases combined. Image Attachments Martin Jönsson CEO And Pontus Forsell Head Of Discovery And Research AlzeCure Pharma 2023 Attachments AlzeCure presents new preclinical data with NeuroRestore ACD856 at leading Alzheimer's conference SOURCE: AlzeCure Pharma View the original press release on accesswire.com