لخّصلي

خدمة تلخيص النصوص العربية أونلاين،قم بتلخيص نصوصك بضغطة واحدة من خلال هذه الخدمة

نتيجة التلخيص (50%)

3.Utilizing endogenous transport systems to ferry therapeutic agents across the BBB is an active area of research.These findings indicate that under conditions of neuroinflammation and BBB dysfunction, the absence of these genes exacerbates both peripheral and CNS inflammation, highlighting the significance of the immune system and the crosstalk between the periphery and the CNS in PD. In a three-dimensional model replicating the BBB, it was noted that astrocytes carrying the LRRK2 G2019S mutation displayed a pro-inflammatory profile and induced changes in the morphology and function of brain blood vessels [46].Several clinical studies, including functional imaging of human patients, analysis of postmortem brain specimens, permeability assessments of drugs used for PD treatment, analysis of albumin/IgG levels in the CSF, and animal models induced with toxins, have identified diverse pathological mechanisms responsible for disrupting the BBB [47].Blood-Brain Barrier and Blood-Cerebrospinal Barrier in PD The blood-brain barrier (BBB), composed of brain endothelial cells, and the blood- CSF barrier (BCSF), formed by the tight junctions between choroid plexus epithelial cells, are two crucial anatomical barriers that constitute the primary interface between the extracellular fluids of the brain and the bloodstream [45].Specifically, in PARKIN and PINK1 knockout mice subjected to active EAE, an animal model of neuroinflammation characterized by disrupted BBB, there was a reduced number of astrocyte cells observed during the later chronic stages of the disease, especially in aged mice [24,26].This oxidative stress harms intercellular junctions, contributes to abnormal cerebral angiogenesis, results in neurovascular decoupling, and actively participates in and exacerbates vascular inflammation [48].While it remains uncertain whether BBB dysfunction is an early event or a consequence of the primary insult in these diseases, it appears that astrocytes play a pivotal role in connecting the pathological processes occurring in the CNS and the periphery through a compromised BBB.These barriers serve as the foremost guardians, not only regulating the passage of various circulating substances between brain fluids and blood but also governing interactions between the peripheral immune system and the CNS [45].Further examination of postmortem human brain tissue confirmed that the vascular characteristics observed in the in vitro model closely corresponded to alterations seen in the brains of individuals with sporadic PD [46].Several therapeutic approaches are being explored to target the BBB and BCSF barrier in PD. Lipid and polymeric-based nanoparticles can be engineered to encapsulate therapeutic agents and navigate the BBB.Among the factors contributing to BBB disruption, notable attention has been directed toward phenotypic changes in astrocytes and endothelial cells, which, together with pericytes, constitute the neurovascular unit [47].Similarly, DJ-1 deficiency can disrupt astrocyte-mediated repair processes through the destabilization of Sox9 and impair the astrogliosis response [52].Dysfunctional astrocytes were observed in PD genetic animal models.


النص الأصلي


  1. Blood–Brain Barrier and Blood–Cerebrospinal Barrier in PD
    The blood–brain barrier (BBB), composed of brain endothelial cells, and the blood– CSF barrier (BCSF), formed by the tight junctions between choroid plexus epithelial cells, are two crucial anatomical barriers that constitute the primary interface between the extracellular fluids of the brain and the bloodstream [45]. These barriers serve as the foremost guardians, not only regulating the passage of various circulating substances between brain fluids and blood but also governing interactions between the peripheral immune system and the CNS [45]. The malfunction of the blood–CSF barrier and, particularly the BBB, has been associated with the initiation and progression of numerous neurological disorders, including PD [46]. Several clinical studies, including functional imaging of human patients, analysis of postmortem brain specimens, permeability assessments of drugs used for PD treatment, analysis of albumin/IgG levels in the CSF, and animal models induced with toxins, have identified diverse pathological mechanisms responsible for disrupting the BBB [47]. These mechanisms include the breakdown of intercellular junctions, the accumulation of toxic substances, vascular inflammation, and oxidative stress. Among the factors contributing to BBB disruption, notable attention has been directed toward phenotypic changes in astrocytes and endothelial cells, which, together with pericytes, constitute the neurovascular unit [47].
    Mitochondrial oxidative stress within brain endothelial cells emerges as a critical factor in multiple pathological processes responsible for BBB disruption [48]. This oxidative stress harms intercellular junctions, contributes to abnormal cerebral angiogenesis, results in neurovascular decoupling, and actively participates in and exacerbates vascular inflammation [48].
    Moreover, the precise role of reactive astrogliosis in the pathogenesis of PD is not fully understood, although it seems to be linked to alterations in BBB permeability [49]. Reactive astrogliosis, often accompanied by neuronal death, can result from various insults to the brain, including infection, inflammatory processes, trauma, α-syn accumulation, and ischemia [50]. Conversely, mutations in the PARKIN gene are associated with alterations in astrocytes, suggesting the potential involvement of an astrocyte-related mechanism influencing non-autonomous cell death [51]. Similarly, DJ-1 deficiency can disrupt astrocyte-mediated repair processes through the destabilization of Sox9 and impair the astrogliosis response [52]. Dysfunctional astrocytes were observed in PD genetic animal models. Specifically, in PARKIN and PINK1 knockout mice subjected to active EAE, an animal model of neuroinflammation characterized by disrupted BBB, there was a reduced number of astrocyte cells observed during the later chronic stages of the disease, especially in aged mice [24,26]. These findings indicate that under conditions of neuroinflammation and BBB dysfunction, the absence of these genes exacerbates both peripheral and CNS inflammation, highlighting the significance of the immune system and the crosstalk between the periphery and the CNS in PD.
    In a three-dimensional model replicating the BBB, it was noted that astrocytes carrying the LRRK2 G2019S mutation displayed a pro-inflammatory profile and induced changes in the morphology and function of brain blood vessels [46]. Further examination of postmortem human brain tissue confirmed that the vascular characteristics observed in the in vitro model closely corresponded to alterations seen in the brains of individuals with sporadic PD [46].
    While it remains uncertain whether BBB dysfunction is an early event or a consequence of the primary insult in these diseases, it appears that astrocytes play a pivotal role in connecting the pathological processes occurring in the CNS and the periphery through a compromised BBB.
    Regarding the BCSF barrier, our understanding of its involvement in regulating alpha-synuclein levels in the CSF is limited. A study suggested that the choroid plexus can facilitate the transport of α-syn between the blood and the CSF [32375819]. However, another group observed no dysfunction of the BCSF barrier or indications of local IgG synthesis in the early stages of PD [53]. Several therapeutic approaches are being explored to target the BBB and BCSF barrier in PD. Lipid and polymeric-based nanoparticles can be engineered to encapsulate therapeutic agents and navigate the BBB. Surface modifications can enhance their ability to cross the barrier and release the payload in the brain. Some studies have investigated the use of dopamine or levodopa-loaded nanoparticles to deliver neuroprotective agents or anti-inflammatory drugs to the brain in PD [54,55]. Focused ultrasound is a non-invasive technique that uses ultrasound waves to temporarily disrupt the BBB, allowing for enhanced drug delivery. This approach has shown promise in preclinical studies for delivering therapeutic agents to specific brain regions affected by PD [56]. Intranasal administration provides a non-invasive route for drug delivery to the brain. Certain substances can bypass the BBB through the olfactory and trigeminal pathways, reaching the brain directly from the nasal cavity [57]. Studies have explored the intranasal delivery of neuroprotective agents and other drugs for potential PD treatment [58]. Utilizing endogenous transport systems to ferry therapeutic agents across the BBB is an active area of research. This involves designing drugs or drug carriers that can hijack existing transport mechanisms, aiming to enhance the specificity and efficiency of drug delivery while minimizing potential side effects [59]. Peptides that can target specific receptors on the BBB have been investigated for their potential to facilitate drug transport across the barrier. These peptides can be conjugated to therapeutic agents to enhance their ability to cross the BBB [60]. Biologics, including antibodies and other large molecules, are being engineered to improve their ability to cross the BBB by modifying their structure. These biologics may target specific pathways involved in PD pathology [61]. These diverse strategies represent a dynamic field of research with the potential to advance the development of more effective and targeted therapies for PD.


تلخيص النصوص العربية والإنجليزية أونلاين

تلخيص النصوص آلياً

تلخيص النصوص العربية والإنجليزية اليا باستخدام الخوارزميات الإحصائية وترتيب وأهمية الجمل في النص

تحميل التلخيص

يمكنك تحميل ناتج التلخيص بأكثر من صيغة متوفرة مثل PDF أو ملفات Word أو حتي نصوص عادية

رابط دائم

يمكنك مشاركة رابط التلخيص بسهولة حيث يحتفظ الموقع بالتلخيص لإمكانية الإطلاع عليه في أي وقت ومن أي جهاز ماعدا الملخصات الخاصة

مميزات أخري

نعمل علي العديد من الإضافات والمميزات لتسهيل عملية التلخيص وتحسينها


آخر التلخيصات

يهدف إلى دراسة ...

يهدف إلى دراسة الأديان كظاهرة اجتماعية وثقافية وتاريخية، دون الانحياز إلى أي دين أو تبني وجهة نظر مع...

‏تعريف الرعاية ...

‏تعريف الرعاية التلطيفية‏ ‏وفقا للمجلس الوطني للصحة والرفاهية ، يتم تعريف الرعاية التلطيفية على النح...

Risky Settings ...

Risky Settings Risky settings found in the Kiteworks Admin Console are identified by this alert symb...

الممهلات في الت...

الممهلات في التشريع الجزائري: بين التنظيم القانوني وفوضى الواقع يخضع وضع الممهلات (مخففات السرعة) عل...

Lakhasly. (2024...

Lakhasly. (2024). وتكمن أهمية جودة الخدمة بالنسبة للمؤسسات التي تهدف إلى تحقيق النجاح والاستقرار. Re...

‏ Management Te...

‏ Management Team: A workshop supervisor, knowledgeable carpenters, finishers, an administrative ass...

تسجيل مدخلات ال...

تسجيل مدخلات الزراعة العضوية (اسمدة عضوية ومخصبات حيوية ومبيدات عضوية (حشرية-امراض-حشائش) ومبيدات حي...

My overall expe...

My overall experience was good, but I felt like they discharged me too quickly. One night wasn't eno...

- لموافقة المست...

- لموافقة المستنيرة*: سيتم الحصول على موافقة مستنيرة من جميع المشاركين قبل بدء البحث. - *السرية*: سي...

تعزيز الصورة ال...

تعزيز الصورة الإيجابية للمملكة العربية السعودية بوصفها نموذجًا عالميًا في ترسيخ القيم الإنسانية ونشر...

وصف الرئيس الأم...

وصف الرئيس الأمريكي دونالد ترامب، مساء الثلاثاء، الأوضاع الإنسانية في قطاع غزة بأنها "مأساوية"، متعه...

Mears (2014) A ...

Mears (2014) A system of justice that could both punish and rehabilitate juvenile criminals was the ...