Lady GABA Part 2 of 4
Published 12/19/2022
Previously, we talked about the overview of PD, as well as its pathophysiology. Here, we'll be talking about dopamine deficiency and also where GABA starts to come in:
PD is a neurodegenerative disease characterized in part by progressive degeneration of dopamine-producing neurons in the basal ganglia, including the substantia nigra. The role of dopamine deficiency in PD as a result of dopaminergic denervation has been known for decades.. Dopamine deficiency is often treated with drugs and supplements, notably levodopa/carbidopa, which is a well-tolerated dopamine replacement. (1)
But despite this, and multiple other pharmacologic treatments available, such as dopamine agonists including topical rotigotine (Neupro®) (2), MAO-B inhibitors, COMT inhibitors, and anticholinergics, current treatments are just not enough; as the disease progresses, the medications on the market simply can't control the symptoms effectively or they have disabling side effects, such as motor fluctuations, (3) including dyskinesia. (4) However, degeneration of nondopaminergic neurons is also implicated in many motor and nonmotor symptoms.
This is where GABA comes in. The striatal output system is mediated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), in which GABA has been found to play a neuroprotective role in PD. (5) One concept, deemed the GABA collapse hypothesis, suggests that GABA may be highly significant in PD, as within the central nervous system (CNS) the homeostasis between Ca(2+) and GABA may be responsible for stability across all neuronal functions, both systemically and at the cellular level. Where this applies to PD is that according to this hypothesis, we would need to integrate the slowing or halting of the progression of Ca(2+)/GABA homeostatic perturbation, as it is this perturbation that results autodestruction and therefore, a cascade of irreversible, progressive brain damage and lewy body deposits that cause PD. (6)
But enticing as it is, this hypothesis is not yet proven. So let’s look at the currently known effects of GABA, its metabolites, and how these may help in PD.
More on this in part III.
References
2- Parkinson’s ORD UK: Parkinson's drugs
3- LeWitt-2011
4- Columbia University Irving Medical Center: Major Complication of Parkinson’s Therapy Explained
5- NCBI NLM: Parkinson’s Disease, the Dopaminergic Neuron and Gammahydroxybutyrate
6- PubMed NCBI NLM: Parkinson's Disease and Neurodegeneration: GABA-Collapse Hypothesis