Proteomics

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Memantine administration enhances glutamatergic and GABAergic pathways in human hippocampus of Alzeimer´s disease patients


ABSTRACT: Alzheimer´s disease (AD) represents a serious health, social and economic problem. One of the traditional treatment is administration of memantine, the NMDA receptor antagonist. In this study we investigated how memantine medication impacts protein expression in hippocampus of AD patients using TMT-based quantitative proteomics applied on formalin-fixed paraffin embedded post mortem tissues. The presented dataset shows that memantine treatment has minor but distinct effect on protein expression. While memantine did not prevented general decline of mitochondrial proteome seen in unmedicated AD patients, the treatment selectively induced levels of several mitochondrially-encoded proteins. Furthermore, memantine medication mitigated proteomic pattern of activated phagocytes and enhanced expression of synaptic components involved in both inhibitory (GABA) and excitatory (glutamate) neurotransmission. The upregulation was specific for proteins for which glutamate/GABA serves as a ligand or a substrate (i.e. receptors, transporters, enzymes, etc.), without affecting neuronal nor post-synaptic density markers. This may indicate that memantine-associated effects on glutamatergic and GABAergic is a reaction to memantine-mediated changes of glutamate and GABA levels.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hippocampus

DISEASE(S): Alzheimer's Disease

SUBMITTER: Ivo Fabrik  

LAB HEAD: Ondrej Soukup

PROVIDER: PXD052958 | Pride | 2026-02-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
FragPipe_output.zip Other
RK114_IF232_2D_TMT_0p8ug_M1_A_01.raw Raw
RK114_IF232_2D_TMT_0p8ug_M1_A_02.raw Raw
RK114_IF232_2D_TMT_0p8ug_M1_B_01.raw Raw
RK114_IF232_2D_TMT_0p8ug_M1_B_02.raw Raw
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Publications

Memantine Administration Enhances Glutamatergic and GABAergic Pathways in the Human Hippocampus of Alzheimer's Disease Patients.

Fabrik Ivo I   Kupcik Rudolf R   Fabrikova Daniela D   Chvojkova Marketa M   Holubova Kristina K   Hakenova Kristina K   Horak Martin M   Soukup Jiri J   Manethova Monika M   Rusina Robert R   Matej Radoslav R   Ryska Ales A   Soukup Ondrej O  

Proteomics 20250709 15


One of the traditional treatments in Alzheimer's disease (AD) is administration of memantine, the NMDA receptor antagonist. However, the molecular mechanism of the complex memantine action and the impact on the hippocampal proteome in humans is unknown. In this study, hippocampal proteins extracted from formalin-fixed paraffin-embedded post mortem tissues obtained from healthy donors (n = 15), AD patients not treated with memantine (n = 11), and AD patients treated with memantine (n = 8) were in  ...[more]

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