Neurodegenerative Processes in Epilepsy

*Neurodegenerative Diseases - Molecular Mechanisms and Current Therapeutic Approaches*

brain is an early molecular consequence of infection by scrapie prions. Brain Research. 1995;**681**(1-2):235-241

[63] Bouzamondo-Bernstein E et al. The neurodegeneration sequence in prion diseases: Evidence from functional, morphological and

2004;**63**(8):882-899

ultrastructural studies of the GABAergic system. Journal of Neuropathology and Experimental Neurology.

[64] Fang C et al. A neuronal culture system to detect prion Synaptotoxicity. PLoS Pathogens. 2016;**12**(5):e1005623

neurotransmission in cerebellar granule neurons by impairing membrane delivery of VGCC alpha(2)delta-1 subunit. Neuron. 2012;**74**(2):300-313

[66] Dossena S et al. Mutant prion protein expression causes motor and memory deficits and abnormal sleep patterns in a transgenic mouse model.

Neuron. 2008;**60**(4):598-609

[67] Chu NK et al. A C-terminal membrane anchor affects the

interactions of prion proteins with lipid membranes. The Journal of Biological Chemistry. 2014;**289**(43):30144-30160

[68] Alier K et al. Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons. Journal of Neuroscience Research. 2010;**88**(10):2217-2227

[65] Senatore A et al. Mutant PrP suppresses glutamatergic

[54] Weckhuysen D et al. Genetic Creutzfeldt-Jakob disease

mimicking chronic inflammatory demyelinating polyneuropathy. Neurology Neuroimmunology & Neuroinflammation. 2015;**2**(6):e173

[55] Baiardi S et al. Prion-related peripheral neuropathy in sporadic Creutzfeldt-Jakob disease. Journal of Neurology, Neurosurgery, and Psychiatry. 2019;**90**(4):424-427

Neuron. 2007;**53**(3):325-335

Science. 1982;**216**:136-144

2016;**539**(7628):217-226

electrophysiological and

Disease. 2006;**22**(2):363-373

[60] Barrow PA et al. Intrinsic physiological and morphological properties of principal cells of the Hippocampus and Neocortex in hamsters infected with Scrapie. Neurobiology of Disease.

1999;**6**:406-423

2008;**82**(20):9890-9899

[56] Mallucci GR et al. Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice.

[57] Pruisner SB. Novel proteinaceous infectious particles cause scrapie.

[58] Collinge J. Mammalian prions and their wider relevance in

[59] Chiti Z et al. An integrated, temporal study of the behavioural,

neuropathological consequences of murine prion disease. Neurobiology of

[61] Trifilo MJ et al. Scrapie-induced defects in learning and memory of transgenic mice expressing anchorless prion protein are associated with alterations in the gamma aminobutyric acid-ergic pathway. Journal of Virology.

[62] Lu P, Sturman JA, Bolton DC. Altered GABA distribution in hamster

neurodegenerative diseases. Nature.

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**Chapter 11**

**Abstract**

discovery.

**1. What is epilepsy?**

Molecular Mechanisms behind

Initiation of Focal Seizure

Computational Study

**Keywords:** temporal lobe epilepsy, focal seizures

in Temporal Lobe Epilepsy:

*Ruchi Jakhmola Mani and Deepshikha Pande Katare*

Epilepsy is a noncommunicable disease of the brain that affects people of all ages. The chapter aims to identify protein targets and their mechanism of action behind temporal lobe epilepsy. Differentially expressed proteins in temporal lobe epilepsy (TLE) were used to derive a hypothesis demonstrating routes of protein interactions causing focal seizure and identification of putative target receptor for its treatment. Text mining was done by constructing a Boolean query with keywords such as temporal lobe epilepsy, focal seizures, proteomics, etc., in different scientific search engines. The proteins were further used for creating protein interaction network and analysed for their role in focal epileptic seizure pathway. The most appropriate route for initiation of seizure was observed to be route 3. It describes the dysregulated signal transduction from adenosine A1 receptor (ADORA1) to gamma-aminobutyric acid (GABA) B receptor 1 (GABBR1). This causes electrical imbalance and hyper-excitation of neurons that lead to focal seizure. The study also predicts that YWHAZ (3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta) could be the potential target for preventing focal seizures. The network framed in this study is ideal for studying the cascades of events that may occur during focal seizures in TLE and is useful in drug

Epilepsy is the world's fourth most common neurological disorders. As indicated by the International League Against Epilepsy (ILAE), seizure is a transient of signs or appearances on the account of irregular, over the top, or synchronous neuronal development in the cerebrum. According to the WHO, 50 million people worldwide have epilepsy, and it is the fourth most common disease after Alzheimer's [1]. Epilepsy is an electrical unevenness in the cerebrum because of a few reasons like inactive way of life, hereditary distortions, hypoxic conditions, cranial harm, aggravation, or expansion in oxidative anxiety levels in the body, et cetera. A seizure is a sudden surge of electrical movement in the cerebrum. Seizures control how a man shows up or represents a brief span period. Neuronal cells either energize or repress

#### **Chapter 11**
