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The role of molecular chaperones in the mechanisms of epileptogenesis

  • Perspective and Reflection Article
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

Epilepsy is a group of neurological diseases which requires significant economic costs for the treatment and care of patients. The central point of epileptogenesis stems from the failure of synaptic signal transmission mechanisms, leading to excessive synchronous excitation of neurons and characteristic epileptic electroencephalogram activity, in typical cases being manifested as seizures and loss of consciousness. The causes of epilepsy are extremely diverse, which is one of the reasons for the complexity of selecting a treatment regimen for each individual case and the high frequency of pharmacoresistant cases. Therefore, the search for new drugs and methods of epilepsy treatment requires an advanced study of the molecular mechanisms of epileptogenesis. In this regard, the investigation of molecular chaperones as potential mediators of epileptogenesis seems promising because the chaperones are involved in the processing and regulation of the activity of many key proteins directly responsible for the generation of abnormal neuronal excitation in epilepsy. In this review, we try to systematize current data on the role of molecular chaperones in epileptogenesis and discuss the prospects for the use of chemical modulators of various chaperone groups’ activity as promising antiepileptic drugs.

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Abbreviations

ABC:

The ATP-binding cassette transporter

ADLTLE:

Autosomal dominant lateral temporal lobe epilepsy

AEDs:

Antiepileptic drugs

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ATP:

Adenosine triphosphate

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotrophic factor

CHIP:

C terminus of HSC70-interacting protein

CNS:

Central nervous system

CREB:

CAMP response element-binding protein

EAAT:

Excitatory amino acid transporter

EEG:

Electroencephalogram

ER:

Endoplasmic reticulum

ERAD:

ER-associated protein degradation system

FDA:

Food and Drug Administration

GABA:

γ-Aminobutyric acid

GAD:

Glutamate decarboxylase

GC:

Glucocorticoids

GLAST:

Glutamate aspartate transporter

GLT:

Glutamate transporter

GLUT:

Glucose transporter

GR:

Glucocorticoid receptor

Grps:

Glucose-regulated proteins

HS:

Heat shock

HSF:

Heat shock factor

Hsps:

Heat shock proteins

IkB:

Inhibitor of nuclear factor kappa B

JNK:

C-Jun N-terminal kinases

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MDR1:

Multidrug resistance factor 1

MMP:

Matrix metalloproteinases

NF-κB:

Nuclear factor kappa B

NMDA:

N-methyl-D-aspartate

PDI:

Protein disulfide isomerase

PXR:

Pregnane X receptor

SE:

Status epilepticus

TLR:

Toll-like receptor

TLE:

Temporal lobe epilepsy

TNF:

Tumor necrosis factor

UPS:

Ubiquitin-proteasome system

WHO:

World Health Organization

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Funding

The work was funded by the grants of the Russian Science Foundation No. 19–14-00167 (to D.G) and No. 17–74-300–30 (to M.E.).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology RAS, 119991, Moscow, Russia

    Artem I. Davletshin, Anna A. Matveeva, Michael B. Evgen’ev & David G. Garbuz

  2. Moscow Institute of Physics and Technology, 141700, Dolgoprudny, Moscow Region, Russia

    Anna A. Matveeva

  3. Biology Department, Lomonosov Moscow State University, 119991, Moscow, Russia

    Inga I. Poletaeva

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  1. Artem I. Davletshin
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Davletshin, A.I., Matveeva, A.A., Poletaeva, I.I. et al. The role of molecular chaperones in the mechanisms of epileptogenesis. Cell Stress and Chaperones 28, 599–619 (2023). https://doi.org/10.1007/s12192-023-01378-1

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