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    Neurodegenerative diseases and brain delivery of therapeutics: Bridging the gap using dendrimers
    (Editions de Sante, 2023-08-26T00:00:00) Kaur, Amandeep; Singh, Navneet; Kaur, Harmanpreet; Kakoty, Violina; Sharma, Deep Shikha; Khursheed, Rubiya; Babu, Molakpogu Ravindra; Harish, Vancha; Gupta, Gaurav; Gulati, Monica; Kumar, Puneet; Dureja, Harish; Alharthi, Nahed S.; Khan, Farhan R.; Rehman, Zia ur; Hakami, Mohammed Ageeli; Patel, Mrunali; Patel, Rashmin; Zandi, Milad; Vishwas, Sukriti; Dua, Kamal; Singh, Sachin Kumar
    Neurodegenerative diseases (NDs) continue to burden human lives and economic conditions. They continue to challenge the healthcare system due to the associated physiological barriers. Traditional treatment approaches are associated with symptomatic relief and are ineffective in the long run. Dendrimers stand out amongst other nanocarriers due to ease of surface modifications, internal encapsulation, and nanoscale uniformity of the molecule. Moreover, their internal core can encapsulate drug through electrostatic interactions. These are stable carriers in the nanometer size range. These either act as therapeutic agents per se or deliver the target drug across the blood-brain barrier while minimizing toxicity. Emerging as a promising non-invasive approach, they demonstrate the capability to interfere with in-vivo protein aggregation, typically associated with neurodegeneration. They assist via exerting various neuroprotective roles, such as in oxidative stress, neuroinflammation, inhibiting certain biochemical parameters, altering protein misfolding and aggregation, etc. However, certain limitations are associated with their elimination and cytotoxicity. The investigation revealed the masking of exposed cationic surfaces of dendrimers with inert substances, such as polyethylene glycol to limit their cytotoxicity. This review describes the incidences and pathophysiology of several NDs, properties, and methods of dendrimer synthesis, followed by various research to explore dendrimers potential to treat NDs. � 2023 Elsevier B.V.
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    Brain metastasis in breast cancer: focus on genes and signaling pathways involved, blood�brain barrier and treatment strategies
    (Springer Science and Business Media Deutschland GmbH, 2023-03-10T00:00:00) Chhichholiya, Yogita; Ruthuparna, Malayil; Velagaleti, Harini; Munshi, Anjana
    Breast cancer�(BC) is one of the most prevalent types of cancer in women. Despite advancement in early detection and efficient treatment, recurrence and metastasis continue to pose a significant risk to the life of BC patients. Brain metastasis�(BM) reported in 17�20 percent of BC patients is considered as a major cause of mortality and morbidity in these patients. BM includes various steps from primary breast tumor to secondary tumor formation. Various steps involved are primary tumor formation, angiogenesis, invasion, extravasation, and brain colonization. Genes involved in different pathways have been reported to be associated with BC cells metastasizing to the brain. ADAM8 gene, EN1 transcription factor, WNT, and VEGF signaling pathway have been associated with primary breast tumor; MMP1, COX2, XCR4, PI3k/Akt, ERK and MAPK pathways in angiogenesis; Noth, CD44, Zo-1, CEMIP, S0X2 and OLIG2 are involved in invasion, extravasation and colonization, respectively. In addition, the blood�brain barrier is also a key factor in BM. Dysregulation of cell junctions, tumor microenvironment and loss of function of microglia leads to BBB disruption ultimately resulting in BM. Various therapeutic strategies are currently used to control the BM in BC. Oncolytic virus therapy, immune checkpoint inhibitors, mTOR-PI3k inhibitors and immunotherapy have been developed to target various genes involved in BM in BC. In addition, RNA interference (RNAi) and CRISPR/Cas9 are novel interventions in the field of BCBM where research to validate these and clinical trials are being carried out. Gaining a better knowledge of metastasis biology is critical for establishing better treatment methods and attaining long-term therapeutic efficacies against BC. The current review has been compiled with an aim to evaluate the role of various genes and signaling pathways involved in multiple steps of BM in BC. The therapeutic strategies being used currently and the novel ones being explored to control BM in BC have also been discussed at length. � 2023, The Author(s), under exclusive licence to Federaci�n de Sociedades Espa�olas de Oncolog�a (FESEO).