Neurological Disorders: Therapeutics and Diagnostics Targets

What is Neurological disorders

Neurological disorders can be defined as dmg or abnrmal functioning of the nervous system which entails the brain, spinal cord, and other nerves. These disorders are diverse in that they can affect a person’s ability to move, speak, think and otherwise process information. They are diseases marked by the steady and escalating loss or injury of neurons and other nervous system components, which then result in the manifestations and the risks of the particular disease type.

Neurological disorders can also be termed as “Nervous System Diseases” This is also very inclusive because although they term it as disease that is upon the nervous system it covers all the neurological disorders in their broad entity.

Nervous system diseases can be categorized into several types based on the part of the system they affect:Nervous system diseases can be categorized into several types based on the part of the system they affect:

1. Central Nervous System Diseases:These are on the central nervous system which comprises of the brain and spinal cord. SOME OF THESE ARE MULTIPLE SCLEROSIS, ALZHEIMER’S DISEASE, PARKINSON, BRAIN TUMORS ETC.

2. Peripheral Nervous System Diseases:These influence the peripheral nerves Beyond the brain and spinal chord. Some examples include peripheral neuropathy, guillain-barré syndrome, carpal tunnel syndrome and etc.

3. Autonomic Nervous System Diseases:These influence the division of the nervous system responsible for the automatic functions of the body including the heart rate, blood circulation and digestion. Autonomic dysfunction and multiple system atrophy are some examples of conditions which can cause erectile dysfunction.

Neurological disorders classified by MOA

MOA is another way of categorising neurological disorders and this refers to the biochemical processes which are affected by the neurological disorder. Such classification assists in managing the disease by identifying factors that lead to it and, in the process, creates a basis for developing therapies and a diagnostic approach. The MOA-based classification includes categories such as:The MOA-based classification includes categories such as:

Neurodegenerative Diseases: These include the progressive loss of neurons’ functioning and their morphology. The MOA is normally associated with the deposition of toxic proteins, elevated generation of reactive oxygen species, mitochondrial dysfunction, and inflammation. Some examples of degenerative diseases of the nervous system are Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.

Demyelinating Diseases: In these conditions, myelin sheath, the protective covering of nerve fibers present in the brain and spinal cord is destroyed and this interferes with transportation of nerve impulses. This can be due to autoimmune response that occurs when the body attacks the body tissues it is suppose to protect, genetic factors or can be of unknown origin. It is worthy of note that multiple sclerosis is a good example of demyelinating disease.

Neuropathies (Peripheral Nerve Disorders): These diseases are of peripheral nerves and are provoked by mechanical injury; metabolic disorders; infections, and toxins. Most of the time, the action of the MOA includes direct nerve injury or demyelination. They include diabetic neuropathy and Guillain-Barré syndrome.

Vascular Disorders: These include diseases that are disseminated in the blood vessels of the nervous system as stroke or certain transient ischemic attack (TIA). The MOA also embraces blockage in the arteries that supply blood to the brain ( ischemic stroke) or rupture of blood vessels in the brain (ahaemorrhagic)..

Infectious Diseases: These diseases are due to pathogen agents like bacteria, virus, fungi, or parasites in which diseases of nervous system are produced by direct infection to the system or by inflammation as well as damage of nervous tissue. These diseases may include the following; meningitis, encephalitis, and neurosyphilis.

Functional Disorders: These are disorders that affect the nervous system and the tissues and it is not possible to see the changes in the body or in the images. The MOA can be mediated through changes in neural firing in the brain or alteration of the neurotransmitter concentrations. Some of them include migraine, fibromyalgia and functional neurological disorder (FND).

Genetic and Developmental Disorders: These include those that appear at birth or develop as a consequence of a mutation that has occurred in genes. However, the MOA may differ and usually entail abnormalities of genes that are essential in the development, functioning and repair of the neurons. Some are Down’s syndrome, spinal muscular atrophy, phenyl ketonuria (PKU) among others.

Therapeutics and Diagnostics Targets of Neurological disorders

Biomarkers are essential in the identification, evaluation and studying of the outcomes of diseases. These underlying MOA that may be used in classifying nervous system diseases can make biomarkers quite distinct as a result of the many types of diseases involved. Here's a list of biomarkers associated with each MOA-based disease category:Here's a list of biomarkers associated with each MOA-based disease category:

Neurodegenerative Diseases:

Alzheimer's disease: Amyloid beta (Aβ) peptides, Tau proteins (phosphorylated Tau), and neurofilament light chain (NfL) in Cerebrospinal fluid (CSF) and Blood.

Parkinson's disease: CSF alpha synuclein protein, blood alpha synuclein, saliva alpha synuclein; decreased DAT signal in basal ganglia.

Huntington's disease: The biomarkers used were the levels of Mutant Huntingtin (mHTT) protein and neurofilament light chain (NfL) in both CSF and blood.

Demyelinating Diseases:

Multiple sclerosis (MS): Proteins within CSF that show increased turnover, IgG-synthesis and oligoclonal bands, NfL as an indicator of axonal damage and MBP for demyelination.

Neuropathies (Peripheral Nerve Disorders):

Diabetic neuropathy: High blood sugar, increased levels of HbA1c and reduction in nerve fiber density by using skin biopsy.

Guillain-Barré syndrome: Abnormality of CSF: presence of protein in CSF in larger amounts than would normally be anticipated and absence of corresponding white blood cells known as albuminocytologic dissociation.

Vascular Disorders:

Stroke: Diagnostic imaging for ischemic stroke and hemorrhagic stroke includes Computed tomography (CT) and magnetic resonance imaging (MRI) Blood biomarkers are fibrinogen levels, D-dimer and Brain natriuretic peptide (BNP).

Infectious Diseases:

Meningitis: Leukocyte count > 5/x 10(6)/L; increased protein and decreased glucose in CSF; identification of an etiologic agent in CSF culture or PCR.

Encephalitis: PCR for pathogens in the CSF or culture and/or serology for the same pathogens in the serum or CSF.

Functional Disorders:

Migraine: At present there are no biomarkers to diagnose the disease; the attention is paid to determination of CGRP (calcitonin gene-related peptide) level during the attacks.

Fibromyalgia: High concentration of substance P in CSF, abnormally activated regions in fMRI are signifying that patients with fibromyalgia can experience enhanced painful stimuli.

Genetic and Developmental Disorders:

Down syndrome: The technique that presents with structural detail on the chromosome such as chromosomal analysis that depicts an additional chromosome 21.

Spinal muscular atrophy (SMA): Direct testing for deletion or mutations of the SMN1 gene.

Phenylketonuria (PKU): High blood phenylalanine content.

Comprehensive Overview of Therapeutics, Diagnostics, and Biomarkers for Neurological Conditions

Category	Condition	Therapeutics	Diagnostics	Biomarkers	Target ID
Neurodegenerative Diseases	Alzheimer's Disease (AD)	Cholinesterase inhibitors, NMDA receptor antagonists, amyloid beta targeting treatments like aducanumab.	PET scans for amyloid and tau, CSF analysis for amyloid beta, total tau, and phosphorylated tau.	Amyloid beta (APP), Tau protein	GM-T87024, GM-T45593
	Parkinson's Disease (PD)	Dopamine precursors (levodopa), dopamine agonists, MAO-B inhibitors.	Clinical assessment, DAT imaging.	Alpha-synuclein, Dopamine transporter (SLC6A3)	GM-T03644, GM-T55959
Demyelinating Diseases	Multiple Sclerosis (MS)	Immunomodulatory drugs, monoclonal antibodies, oral treatments.	MRI, CSF analysis for oligoclonal bands, neurofilament light chain.	Myelin basic protein (MBP)	GM-T54761
Neuropathies (Peripheral Nerve Disorders)	Diabetic Neuropathy	Blood glucose control, pain management.	Clinical examination, nerve conduction studies.	-
	Guillain-Barré Syndrome (GBS)	IVIG, plasmapheresis.	Clinical presentation, NCV tests, CSF analysis.	-
Vascular Disorders	Stroke	Thrombolytics for ischemic stroke, control of hypertension for hemorrhagic stroke.	CT, MRI, carotid ultrasound, echocardiography.	-
Infectious Diseases	Meningitis and Encephalitis	Antimicrobial treatment based on the pathogen, corticosteroids.	Lumbar puncture for CSF analysis, PCR, MRI or CT.	-
Functional Disorders	Migraine	NSAIDs, triptans, beta-blockers, CGRP inhibitors.	Primarily clinical diagnosis.	CGRP	GM-T93509
	Fibromyalgia	FDA-approved drugs (duloxetine, milnacipran, pregabalin), pain management.	Based on clinical criteria; widespread pain index and symptom severity scale.	-
Genetic and Developmental Disorders	Down Syndrome	Supportive care, early intervention.	Prenatal screening, chromosomal analysis.	-
	Spinal Muscular Atrophy (SMA)	Gene therapy, antisense oligonucleotides, small molecules.	Genetic testing for SMN1 deletions or mutations.	SMN1	GM-T71907
	Phenylketonuria (PKU)	Dietary management, enzyme replacement therapy.	Newborn screening, genetic testing.	Phenylalanine hydroxylase (PAH)	GM-T76213