Targeting Sigma-1 Receptor: A Promising Strategy in the Treatment of Parkinson's Disease.
Talha SiddiquiLokesh Kumar BhattPublished in: Neurochemical research (2023)
Parkinson's disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta region. Parkinson's disease patients exhibit motor symptoms like tremors, rigidity, bradykinesia/hypokinesia, and non-motor symptoms like depression, cognitive decline, delusion, and pain. Major pathophysiological factors which contribute to neuron loss include excess/misfolded alpha-synuclein aggregates, microglial cell-mediated neuroinflammation, excitotoxicity, oxidative stress, and defective mitochondrial function. Sigma-1 receptors are molecular chaperones located at mitochondria-associated ER membrane. Their activation (by endogenous ligands or agonists) has shown neuroprotective and neurorestorative effects in various diseases. This review discusses the roles of activated Sig-1 receptors in modulating various pathophysiological features of Parkinson's disease like alpha-synuclein aggregates, neuroinflammation, excitotoxicity, and oxidative stress.
Keyphrases
- oxidative stress
- cognitive decline
- traumatic brain injury
- mild cognitive impairment
- chronic kidney disease
- lipopolysaccharide induced
- dna damage
- spinal cord
- end stage renal disease
- depressive symptoms
- single cell
- neuropathic pain
- cognitive impairment
- chronic pain
- binding protein
- spinal cord injury
- single molecule
- pain management
- induced apoptosis
- subarachnoid hemorrhage
- prognostic factors
- cell therapy
- estrogen receptor
- smoking cessation
- endoplasmic reticulum