Microglial Autophagy in Parkinson's Disease

Autophagy is the name given to a collection of maintenance processes responsible for clearing waste and damaged proteins and structures from the cell. Autophagy is implicated in aging. It is thought to become dysfunctional and less efficient in cells in aging tissues. Further, evidence suggests that improved autophagy is an important mechanisms in the slowing of aging produced by calorie restriction and a range of other interventions tested in laboratory species. Here, researchers discuss the relationship between aging and autophagy specifically in the context of Parkinson's disease and the role of inflammatory microglia in the progression of that condition. One might compare this with a very similar paper noted last week.

In a healthy organism, the homeostasis of the central nervous system (CNS) is dependent on the interactions of various nerve cells. However, in the CNS of Parkinson's disease (PD) patients, there is an aberrant build-up of α-synuclein (α-Syn) and a cascade effect of gradual neuronal damage that breaks the appropriate balance, which leads to inflammation in the CNS. Autophagy is an evolutionarily conserved degradation pathway that is responsible for the digestion and recycling of the majority of intracytoplasmic proteins and organelles. Autophagy maintains homeostasis by delivering cytoplasmic materials to the lysosome for degradation. Due to poor autophagy, inappropriately aggregated α-Syn in the CNS of PD patients cannot be removed and accumulated. Overall, dysregulation of autophagy is thought to play an important role in the abnormal aggregation of α-Syn and the exacerbation of Parkinson's disease.

Microglia are CNS-specific immune cells that play an immunological role in the CNS comparable to that of macrophages, interact with neurons, and conduct a variety of tasks in the CNS. Recent research shows that microglial autophagy is involved in the function and regulation of inflammation in the CNS. These findings implied that dysregulation of autophagy in microglia may impact innate immune activities, including phagocytosis and inflammation, which, in turn, contribute to illnesses associated with neuroinflammation. To date, many researchers have considered PD to be a neuroinflammatory disease, and the role of microglial autophagy in the pathophysiology of PD has been a hot issue in the field. In this review, we present and highlight the contribution of microglial autophagy to the pathological mechanism of PD and aimed to determine whether microglial autophagy could be a potential target for therapeutic intervention.

Link: https://doi.org/10.3389/fnagi.2022.1039780


Perhaps use minocycline.
Off patent.
Low side effect profile.
Well tolerated.
Known to have a positive effect on reversing the pro-inflammatory state which is characteristic of just about all elderly brains. Helps maintain the integrity of the BBB and clears away the played-out old microglia to make way for a new crop.

Has been used for depression in the elderly refractory to conventional antidepressants with good results. Also for Parkinsonism.

Problem: Big pharma will not touch it as off patent. Also, no large RCT's.

Solution: do not wait for big pharma. Just do it anyway.

Posted by: JLH at February 18th, 2023 3:28 AM
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