The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington's disease in rats: shifting paradigms in Huntington's disease treatment

被引：0

作者：

Wanas, Hanaa ^{[1
,2
]}

Rabie, Mostafa Adel ^{[3
]}

Aboulhoda, Basma Emad ^{[4
]}

Ramadan, Nagwa Mahmoud ^{[5
]}

Abdelwahab, Sahar ^{[6
]}

Abdallah, Sara Sayed Kadry ^{[6
]}

Ali, Eid Nassar ^{[4
,7
]}

Khayruddeen, Leyan Nasruddeen ^{[7
]}

Elhassan, Yasir Hassan ^{[7
]}

Alghabban, Hadel Mahroos ^{[7
]}

Abdelsalam, Shaimaa Mohamed ^{[8
]}

Khalifa, Amira Karam ^{[1
,9
]}

机构：

[1] Cairo Univ, Fac Med, Dept Med Pharmacol, El Saray St Manial, Cairo 11562, Egypt

[2] Taibah Univ, Coll Pharm, Dept Pharmacol & Toxicol, Madinah, Saudi Arabia

[3] Cairo Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt

[4] Cairo Univ, Fac Med, Dept Med Anat & Embryol, Cairo, Egypt

[5] Cairo Univ, Fac Med, Dept Med Physiol, Cairo, Egypt

[6] Cairo Univ, Fac Med, Dept Med Biochem & Mol Biol, Cairo, Egypt

[7] Taibah Univ, Coll Med, Dept Basic Med Sci, Madinah, Saudi Arabia

[8] Cairo Univ, Fac Med, Dept Anat Pathol, Cairo 11562, Egypt

[9] Nahda Univ, Fac Med, Dept Med Pharmacol, Bani Suwayf 62521, Egypt

来源：

FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES | 2024年 / 10卷 / 01期

关键词：

Huntington's disease; Renin-angiotensin system; Lisinopril; Mitochondrial dysfunction; 3-nitropropionic acid; RENIN-ANGIOTENSIN SYSTEM; ALZHEIMERS-DISEASE; CONVERTING ENZYME; KAPPA-B; MITOCHONDRIAL DYSFUNCTION; COGNITIVE IMPAIRMENT; BRAIN; INHIBITION; PROTEIN; MODEL;

D O I：

10.1186/s43094-024-00724-z

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

BackgroundThe exact pathogenesis of Huntington's disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats.MethodsSixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters.ResultsLisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-kappa B, TNF-alpha, IFN-gamma and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2.ConclusionNotably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD. Lisinopril alleviated the mitochondrial dysfunction and restored redox balance via Nrf2/TFAM signaling.Lisinopril downregulated the inflammatory cytokines (NF-kappa B, TNF-alpha, IFN-gamma and IL-6).Lisinopril upregulated the expression of ACE2/Ang1-7/MAS receptor axis of RAS.Lisinopril activated PI3K/Akt/CREB pathway and evoked the neurogenesis via its downstream product BDNF.Lisinopril could be a future neuroprotective treatment against Huntington disease.

引用

页数：22

共 17 条

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