PMID- 38460902
OWN - NLM
STAT- MEDLINE
DCOM- 20240401
LR  - 20240401
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 826
DP  - 2024 Mar 15
TI  - Glycine transporter-1 inhibition by NFPS promotes neuroprotection against 
      striatal damage models.
PG  - 137715
LID - S0304-3940(24)00092-2 [pii]
LID - 10.1016/j.neulet.2024.137715 [doi]
AB  - The striatum, an essential component of the brain's motor and reward systems, 
      plays a pivotal role in a wide array of cognitive processes. Its dysfunction is a 
      hallmark of neurodegenerative diseases like Parkinson's disease (PD) and 
      Huntington's disease (HD), leading to profound motor and cognitive deficits. 
      These conditions are often related to excitotoxicity, primarily due to 
      overactivation of NMDA receptors (NMDAR). In the synaptic cleft, glycine 
      transporter type 1 (GlyT1) controls the glycine levels, a NMDAR co-agonist, which 
      modulates NMDAR function. This research explored the neuroprotective potential of 
      NFPS, a GlyT1 inhibitor, in murine models of striatal injury. Employing models of 
      neurotoxicity induced by 6-hydroxydopamine (PD model) and quinolinic acid (HD 
      model), we assessed the effectiveness of NFPS pre-treatment in maintaining the 
      integrity of striatal neurons and averting neuronal degeneration. The results 
      indicated that NFPS pre-treatment conferred significant neuroprotection, reducing 
      neuronal degeneration, protecting dopaminergic neurons, and preserving dendritic 
      spines within the striatum. Additionally, this pre-treatment notably mitigated 
      motor impairments resulting from striatal damage. The study revealed that GlyT1 
      inhibition led to substantial changes in the ratios of NMDAR subunits 
      GluN2A/GluN1 and GluN2B/GluN1, 24 h after NFPS treatment. These findings 
      underscore the neuroprotective efficacy of GlyT1 inhibition, proposing it as a 
      viable therapeutic strategy for striatum-related damage.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Izidoro Ribeiro, Raul
AU  - Izidoro Ribeiro R
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania-GO, Brazil.
FAU - Almeida Carvalho, Gustavo
AU  - Almeida Carvalho G
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania-GO, Brazil.
FAU - Almeida Chiareli, Raphaela
AU  - Almeida Chiareli R
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania-GO, Brazil.
FAU - Vieira de Assis Lima, Isabel
AU  - Vieira de Assis Lima I
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
FAU - Quaglio Bellozi, Paula Maria
AU  - Quaglio Bellozi PM
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
FAU - Oliveira-Lima, Onesia Cristina
AU  - Oliveira-Lima OC
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania-GO, Brazil.
FAU - Oliveira Giacomelli, Agatha
AU  - Oliveira Giacomelli A
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo-SP, Brazil.
FAU - Birbrair, Alexander
AU  - Birbrair A
AD  - Departamento de Patologia, Instituto de Ciencias Biologicas, Universidade Federal 
      de Minas Gerais, Belo Horizonte-MG, Brazil.
FAU - Santiago Gomez, Renato
AU  - Santiago Gomez R
AD  - Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte-MG, 
      Brazil.
FAU - Pinheiro de Oliveira, Antonio Carlos
AU  - Pinheiro de Oliveira AC
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
FAU - Ulrich, Henning
AU  - Ulrich H
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo-SP, Brazil.
FAU - Cunha Xavier Pinto, Mauro
AU  - Cunha Xavier Pinto M
AD  - Departamento de Farmacologia, Instituto de Ciencias Biologicas, Universidade 
      Federal de Goias, Goiania-GO, Brazil. Electronic address: pintomcx@ufg.br.
LA  - eng
PT  - Journal Article
DEP - 20240307
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Glycine Plasma Membrane Transport Proteins)
RN  - Z711V88R5F (Sarcosine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Glycine Plasma Membrane Transport Proteins/metabolism
MH  - Sarcosine/pharmacology
MH  - Neuroprotection
MH  - Glycine/pharmacology
MH  - Corpus Striatum/metabolism
MH  - *Huntington Disease/drug therapy
OTO - NOTNLM
OT  - GlyT1 inhibition
OT  - Huntington's disease
OT  - NMDA receptors
OT  - Parkinson's disease
OT  - Striatal damage
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/03/10 00:42
MHDA- 2024/04/01 06:43
CRDT- 2024/03/09 19:20
PHST- 2023/12/24 00:00 [received]
PHST- 2024/03/04 00:00 [revised]
PHST- 2024/03/06 00:00 [accepted]
PHST- 2024/04/01 06:43 [medline]
PHST- 2024/03/10 00:42 [pubmed]
PHST- 2024/03/09 19:20 [entrez]
AID - S0304-3940(24)00092-2 [pii]
AID - 10.1016/j.neulet.2024.137715 [doi]
PST - ppublish
SO  - Neurosci Lett. 2024 Mar 15;826:137715. doi: 10.1016/j.neulet.2024.137715. Epub 
      2024 Mar 7.