Cholesterol - A putative endogenous contributor towards Parkinson's disease.
Study Goal
The researchers aimed to review the neuropathological effects of excess cholesterol or its metabolites (oxysterols) in the brain, particularly their contribution to Parkinson's disease (PD), and evaluate the potential of statin therapy in reducing PD occurrence.
Results Summary
The study found that high-fat diet exacerbates parkinsonian pathologies, including dopaminergic neuron loss and oxidative stress in animal PD models, while clinical reports on cholesterol's role in PD showed mixed results (some positive, some negative/no correlation). Oxysterols were noted to cause alpha-synuclein aggregation and dopamine neuron destruction in vitro.
Population
Animal models of PD and in vitro neuronal models; some clinical studies referenced.
Effective Dosage
Not specified
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
oxysterols | increase | alpha-synuclein aggregation and destruction of dopamine containing neurons | in vitro models | - | causing | #1 |
oxysterols | increase | oxidative stress provoking potency | in vitro models | - | direct influence on | #2 |
cholesterol or oxysterol | no change | Parkinsonism | prospective clinical reports | - | negative or no correlation | #3 |
plasma cholesterol | increase | incidence of Parkinson's disease (PD) | prospective clinical studies | - | positive correlation | #4 |
high fat diet | increase | parkinsonian pathologies, including loss of dopaminergic neurons and oxidative stress parameters | animal models of PD | - | exacerbates | #5 |
statin therapy | decrease | reducing the occurrence of PD | - | - | cholesterol lowering efficacy | #6 |
Elevated levels of cholesterol and its metabolites (oxysterols) have been reported to be associated not only with several metabolic syndromes, but also become a prognostic risk factor of neurodegenerative diseases particularly Alzheimer's disease. The incidence and the prospect of Alzheimer's disease with respect to elevated levels of cholesterol have been studied extensively and reviewed earlier. Recently, several interesting findings have shown the occurrence of equivalent Parkinsonian pathologies in cellular neuronal models, mediated by oxysterols or excess exposure to cholesterol. In this regard, oxysterols are particular in causing alpha-synuclein aggregation and destruction of dopamine containing neurons in in vitro models, which is linked to their direct influence on oxidative stress provoking potency. Inspite of the significant in vitro reports, which suggest the relativeness of cholesterol or oxysterol towards Parkinsonism, several prospective clinical reports provided a negative or no correlation. However, few prospective clinical studies showed a positive correlation between plasma cholesterol and incidence of Parkinson's disease (PD). Also, few significant studies have convincingly demonstrated that high fat diet exacerbates parkinsonian pathologies, including loss of dopaminergic neurons and oxidative stress parameters in animal models of PD. The present review brings together all the neuropathological proceedings mediated by excess cholesterol or its metabolites in brain in the light of their contribution towards the onset of PD. Also we have reviewed the possibilities of cholesterol lowering efficacy of statin therapy, in reducing the occurrence of PD.