Neuroproteomics in Epilepsy: What Do We Know so Far?

Abstract

Epilepsies are chronic neurological diseases that affect approximately 2% of the world population. In addition to being one of the most frequent neurological disorders, treatment for patients with epilepsy remains a challenge, because a proportion of patients do not respond to the antiseizure medications that are currently available. This results in a severe economic and social burden for patients, families, and the healthcare system. A characteristic common to all forms of epilepsy is the occurrence of epileptic seizures that are caused by abnormal neuronal discharges, leading to a clinical manifestation that is dependent on the affected brain region. It is generally accepted that an imbalance between neuronal excitation and inhibition generates the synchronic electrical activity leading to seizures. However, it is still unclear how a normal neural circuit becomes susceptible to the generation of seizures or how epileptogenesis is induced. Herein, we review the results of recent proteomic studies applied to investigate the underlying mechanisms leading to epilepsies and how these findings may impact research and treatment for these disorders.

Compartment-specific total RNA profile of Hippocampal and Cortical cells from Mesial Temporal Lobe Epilepsy tissue

“…VIM and GSN are mainly expressed in astrocytes and function as anti-inflammatory and neuroprotective agents. These proteins were reported to be upregulated at the chronic phase of experimental epilepsy and in human mTLE tissue (Bitsika et al, 2016;Bruxel et al, 2021;do Canto et al, 2021). Even though reactive gliosis is observed in mTLE non-HS HC tissue, VIM and GSN displayed lower expression in our dataset (Blümcke et al, 2013).…”

Application of Thermodynamics and Protein–Protein Interaction Network Topology for Discovery of Potential New Treatments for Temporal Lobe Epilepsy

“…In particular, the altered molecular pathways result in a variety of modifications in voltage-gated and receptor gated ion channels that lead to a perturbation of dendritic excitability [12]. Neuroproteomic studies on epilepsy revealed a significant contribution of proteins involved in energy metabolism, oxidative stress, inflammation, and excitatory imbalance [63]. Here, we report the results of our systems-biology based investigation, which analyzed the Gibbs Homology network for protein-protein interaction epilepsy data at threshold 32.…”

Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients

“…Firstly, it only allows to obtain the transcript expression profiles and histopathological features at the time of surgery. Secondly, there is no availability of control tissue, since the use of autopsy material, or brain tumor resected tissue, as control is not either feasible or technically adequate 87 . In order to circumvent these limitations several groups 88 , 89 including our own 90 , have recurred to animal models of acquired epilepsy for conducting temporal analyses of brain histological and molecular changes that arise after an initial precipitating injury.…”