As loving standards progressed during the last century, the diet became richer, and health conditions, such as gout, which were usually associated with people with high living standards became increasingly more common.
It was soon recognized that acid uric imbalance was associated, not only with gout, but with a range of diseases. Most striking associations are inverse correlations as they should teach us something.
One such inverse correlation is between elevated acid uric levels and Parkinson's disease. On the contrary, there is an association between low levels of acid uric and patients with Parkinson's disease, or multiple sclerosis. Yet something related to Parkinson's disease may cause low uric acid (reverse causation).
Indeed, Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies and Lewy neurites, which mainly consist of aggregates of α-synuclein. It is believed that α-synuclein aggregates poison the brain's cells and indeed especially this tiny part of the brain named "substantia nigra". Yet like other protein aggregates, they may form to protect the brain against some external aggression or stressing event. So the biological mechanisms underlying α-synuclein relationships with dopaminergic neurons have never been firmly established.
While the most frequently proposed mechanism for uric acid's inverse association with Parkinson's disease is that it is an antioxidant, however, clinical trials aiming to raise uric acid levels failed to slow the progression of Parkinson's disease. Then some scientists argued that many studies have pointed to mitochondrial dysfunction in Parkinson's disease. One of the major functions of mitochondria is producing energy in the form of ATP, which is quantitatively the most abundant of all purines in the body. As serum uric acid is a by-product of purine metabolism, mitochondrial dysfunction, and energy failure in Parkinson's disease may lead to low serum uric acid levels. An excellent review can be found here.
There is ample evidence that neurons can internalize extracellular aggregates by endocytosis. Some studies have shown that acid uric inhibits α-syn endocytosis by neurons thereby limiting the progression of the disease.
To precise the relation between Parkinson's disease and uric acid, a study shows that factors other than the purine metabolic system might influence CSF values of uric acid and that purine recycling pathways may be impaired. enter link description here
The current study found a significant reduction in hypoxanthine and inosine levels in the CSF of patients with PD but not in the serum. This small study, published in Nature Parkinson's Disease Journal, was published in preprints last year. Basically, it confirms previous findings such as those reported in the 2023 review above.