Exploring the Use of Pharmacological Approaches in managing Neurodegenerative Disorders
Neurodegenerative diseases, such as Parkinson's and Alzheimer's, can lead to secondary mental illnesses like anxiety, depression, schizophrenia, psychosis, epilepsy, and bipolar disorder. These conditions affect the brain, spinal cord, and peripheral nerves, which are vital organs that regulate the entire functional processing of the human body.
In Parkinson's disease (PD), the mainstay of pharmacological treatment is levodopa, which restores dopamine levels in the brain and improves motor symptoms. Other treatments include dopamine agonists and enzyme inhibitors like MAO-B and COMT inhibitors. For more advanced stages, continuous drug delivery systems and deep brain stimulation devices are utilised. However, in late stages, some symptoms become resistant to these therapies, highlighting the need for new treatments.
Recent advances in Alzheimer's disease (AD) include monoclonal antibody drugs such as donanemab and lecanemab, which target amyloid-beta protein deposits in the brain. These drugs represent a shift from symptom relief toward modifying the disease process itself. Other experimental and adjunct pharmacological approaches include natural compounds like curcumin, which exhibits neuroprotective effects through anti-inflammatory and antioxidant mechanisms.
Ongoing research also explores metabolic interventions and phytochemical nanoparticles designed to improve drug delivery and bioavailability for neurological disorders, potentially providing new avenues for treating neurodegeneration. The neuropharmacological approach addresses neuronal loss through multiple drug-based approaches, including mechanistic targets within cellular and molecular pathways, symptomatic intervention to restore neurotransmitter levels, early diagnosis and progression of diseases, and monitoring of pharmacotherapy through biomarkers.
In Amyotrophic Lateral Sclerosis (ALS), riluzole prevents the excitotoxic potential of neurons and preserves neuronal function. Melatonin, an anti-inflammatory agent, decreases neuronal injury. Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are used to stabilise mood problems and treat dementia-related degeneration issues. Alzheimer's disease treatment restores the levels of acetylcholine through various methods, including AchE inhibitors and memantine.
Upon ligands binding to PRRs (such as amyloid beta, TLR4, and α-synuclein-TLR2), signal transduction pathways take place, including nuclear factor kappa B and mitogen-activated protein kinase. Microglia, which survey the whole nervous system to find harmful substances and remove them from healthy cells, play a crucial role in these processes. When microglia are damaged, their defensive role is compromised, leading to more oxidative stress and exacerbating neuroinflammation.
The application of the novel strategy by the implementation of personalised medicines targeting neurodegenerative diseases is another approach. Sargramostim changes the microglial state from a pro-inflammatory M1 state to an anti-inflammatory M2, etanercept is a TNF-α inhibitor clinical trial phase 2 drug that inhibits the inflammatory pathway, and leukotriene antagonist montelukast is an anti-inflammatory and is used in Phase II clinical trials for anti-Alzheimer effects.
In summary, current pharmacological treatments for neurodegenerative diseases range from symptomatic dopamine restoration in PD to disease-modifying anti-amyloid antibodies in AD, alongside emerging molecular therapies targeting inflammation, oxidative stress, and protein aggregation pathways. However, challenges remain, especially for advanced stages or other neurodegenerative conditions, underscoring the urgent need for novel therapeutic strategies.
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- In the fight against neurodegenerative diseases, medication like donanemab and lecanemab for Alzheimer's and riluzole for Amyotrophic Lateral Sclerosis are being developed to target specific proteins, aiming to modify the disease process.
- Beyond pharmacological approaches, the application of personalized medicines, such as Sargramostim, Etanercept, and Montelukast in clinical trials, aims to modify the microglial state to reduce inflammation, addressing the defensive role of microglia in neurodegenerative conditions.
- The integration of health-and-wellness practices, like the use of melatonin and selective serotonin reuptake inhibitors (SSRIs), along with deep sleep and relaxation techniques, may complement traditional therapies, contributing to improved overall health in patients with neurodegenerative diseases.
