Liliana Mendieta

Centro de Investigación Biomédica en Red

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Ilhuicamina Daniel Limón

Benemérita Universidad Autónoma de Puebla

José Aguilera

Hospital Universitario Araba

Yousef Tizabi

Howard University

Irving Parra

Benemérita Universidad Autónoma de Puebla

Isabel Martínez‐Alcalá

Universidad Católica San Antonio de Murcia

Edgar Zenteno

Universidad Nacional Autónoma de México

Aleidy Patricio-Martínez

Benemérita Universidad Autónoma de Puebla

Jorge Guevara

Universidad Nacional Autónoma de México

Alfonso Díaz

Benemérita Universidad Autónoma de Puebla

Victorino Alatriste

Benemérita Universidad Autónoma de Puebla

Cooperative Institutions

Benemérita Universidad Autónoma de Puebla

Universidad Nacional Autónoma de México

Autonomous University of Yucatán

Instituto Nacional de Neurología y Neurocirugía

Universidad Autónoma Metropolitana

Universitat Autònoma de Barcelona

Biomedical Research Networking Center on Neurodegenerative Diseases

Center for Research and Advanced Studies of the National Polytechnic Institute

Instituto Politécnico Nacional

Centro de Investigación Biomédica en Red

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Antidepressant and Neuroprotective Effects of 3-Hydroxy Paroxetine, an Analog of Paroxetine in Rats

The International Journal of Neuropsychopharmacology (2022)

Pedro Efraín Hernández-Arrambide Alan Carrasco‐Carballo Irving Parra Delfino Chamorro‐Arenas Isabel Martínez‐Alcalá

Abstract Background Paroxetine (PX) is a widely used antidepressant with side effects such as weakness, dizziness, and trouble sleeping. In search of novel compounds with better efficacy and fewer side effects, we synthesized 3HPX, a hydroxylated analog of PX, and compared the 2 in silico for their pharmacokinetic and binding properties and in vivo for their antidepressant and potential neuroprotective effects. Methods In silico studies compared pharmacological properties as well as interactions of PX and 3HPX with the serotonin transporter. In vivo studies utilized an animal model of comorbid depression-Parkinson disease. Adult male Wistar rats were injected (sterotaxically) with lipopolysaccharide in the striatum (unilaterally), followed by 14 days of once-daily injections (i.p.) of 10 mg/kg PX or 3HPX. Animals were tested for motor asymmetry and locomotor activity as well as indices of anhedonia and helplessness using sucrose preference and forced swim tests, respectively. Brains of these animals were collected after the last test, and tyrosine hydroxylase–positive neurons in substantia nigra pars compacta and Iba-1–positive stained microglia in ipsilateral striatum were measured. Results In silico findings indicated that 3HPX could bind stronger to serotonin transporter and also have a better clearance and hence less toxicity compared with PX. In vivo results revealed a more effective reversal of immobility in the swim test, substantial increase in tyrosine hydroxylase–positive cells in the substantia nigra pars compacta, and more ramified Iba-1+ cells by 3HPX compared with PX. Conclusion The findings suggest superior effectiveness of 3HPX as an antidepressant and neuroprotectant compared with PX and hence potential utility in Parkinson disease depression co-morbidity.

Pars compacta

Paroxetine

10.1093/ijnp/pyac077

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β-Secretase-1: In Silico Drug Reposition for Alzheimer’s Disease

International Journal of Molecular Sciences (2023)

Roberto A. Galeana-Ascencio Liliana Mendieta Ilhuicamina Daniel Limón Dino Gnecco Joel L. Terán

The β-secretase-1 enzyme (BACE-1) performs a key role in the production of beta-Amyloid protein (Aβ), which is associated with the development of Alzheimer’s disease (AD). The inhibition of BACE-1 has been an important pharmacological strategy in the treatment of this neurodegenerative disease. This study aims to identify new potential candidates for the treatment of Alzheimer’s with the help of in silico studies, such as molecular docking and ADME prediction, from a broad list of candidates provided by the DrugBank database. From this analysis, 1145 drugs capable of interacting with the enzyme with a higher coupling energy than Verubecestat were obtained, subsequently only 83 presented higher coupling energy than EJ7. Applying the oral route of administration as inclusion criteria, only 41 candidates met this requirement; however, 6 of them are associated with diagnostic tests and not treatment, so 33 candidates were obtained. Finally, five candidates were identified as possible BACE-1 inhibitors drugs: Fluphenazine, Naratriptan, Bazedoxifene, Frovatriptan, and Raloxifene. These candidates exhibit pharmacophore-specific features, including the indole or thioindole group, and interactions with key amino acids in BACE-1. Overall, this study provides insights into the potential use of in silico methods for drug repurposing and identification of new candidates for the treatment of Alzheimer’s disease, especially those targeting BACE-1.

10.3390/ijms24098164

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Differential Effects of LPS and 6-OHDA on Microglia’s Morphology in Rats: Implications for Inflammatory Model of Parkinson’s Disease

Neurotoxicity Research (2019)

Irving Parra Isabel Martínez‐Alcalá Gabriel Ramirez‐Garcia Yousef Tizabi Liliana Mendieta

Pars compacta

MPTP

10.1007/s12640-019-00104-z

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Citations (21)

Chronic Treatment with the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium lactis BB12 Attenuates Motor Impairment, Striatal Microglial Activation, and Dopaminergic Loss in Rats with 6-Hydroxydopamine-induced Hemiparkinsonism