Mechanisms of Autoimmune Cell in DA Neuron Apoptosis of Parkinson’s Disease: Recent Advancement

Abstract

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that manifests as motor and nonmotor symptoms due to the selective loss of midbrain DArgic (DA) neurons. More and more studies have shown that pathological reactions initiated by autoimmune cells play an essential role in the progression of PD. Autoimmune cells exist in the brain parenchyma, cerebrospinal fluid, and meninges; they are considered inducers of neuroinflammation and regulate the immune in the human brain in PD. For example, T cells can recognize α-synuclein presented by antigen-presenting cells to promote neuroinflammation. In addition, B cells will accelerate the apoptosis of DA neurons in the case of PD-related gene mutations. Activation of microglia and damage of DA neurons even form the self-degeneration cycle to deteriorate PD. Numerous autoimmune cells have been considered regulators of apoptosis, α-synuclein misfolding and aggregation, mitochondrial dysfunction, autophagy, and neuroinflammation of DA neurons in PD. The evidence is mounting that autoimmune cells promote DA neuron apoptosis. In this review, we discuss the current knowledge regarding the regulation and function of B cell, T cell, and microglia as well as NK cell in PD pathogenesis, focusing on DA neuron apoptosis to understand the disease better and propose potential target identification for the treatment in the early stages of PD. However, there are still some limitations in our work, for example, the specific mechanism of PD progression caused by autoimmune cells in mitochondrial dysfunction, ferroptosis, and autophagy has not been clarified in detail, which needs to be summarized in further work.

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

“…As with the gut microbiome, the pineal melatonin optimization of mitochondrial function (partly via the induction of the mitochondrial melatonergic pathway) better enables all cells to resist challenges posed by various stressors, including neighboring cells in a given intercellular microenvironment. There is a growing appreciation that a wide array of diverse medical conditions have 'autoimmune' aspects, such as Parkinson's disease [138] and schizophrenia [139]. The suppression of the mitochondrial melatonergic pathway also has consequences for the regulation of processes underpinning immune-mediated cell loss, classically referred to as 'autoimmunity', including via the regulation of intercellular processes.…”

Infectious Microorganisms Seen as Etiologic Agents in Parkinson’s Disease

“…Myelo-peroxidase, an oxidant-producing enzyme that might harm dopamine neurons, is released by astrocytes, and it has been suggested that astrocytes could control microglial multiplication by releasing the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) [ 34 ]. By contrast, the marked and considerable increase in microglial activation was already consistently seen in PD animal models and Parkinson’s disease postmortem investigations or MPTP-induced parkinsonism [ 35 , 36 , 37 ]. This stimulation and expansion of microglia is known as the neuroinflammatory characteristic of Parkinson’s disease.…”

“…Neuronal damage may need prolonged exposure to proinflammatory cytokines such as IL-1, according to one theory [ 41 ]. On the cell bodies and processes of nigrostriatal neurons exist receptors for proinflammatory cytokines, including TNF-alpha, which probably renders the neurons that are vulnerable to the devastating impacts of cytokines produced by stimulated microglia [ 36 ]. This receptor modulation may begin or activate a caspase cascade, culminating in the neuron’s apoptotic death [ 35 , 36 ].…”

“…It is impossible to demonstrate that every instance of PD is connected with elevated inflammatory processes and concomitant chronic infection. This is owing to numerous variables, along with the notion that not every PD patient exhibits consistent proof of inflammatory cytokine imbalance and that a chronic inflammatory status does not necessarily lead to the onset of PD [ 14 , 36 ]. Those with a genetic susceptibility to Parkinson’s disease can generate the condition as a consequence of an existing immune system imbalance [ 14 , 36 ].…”

LRRK2 Gly2019Ser Mutation Promotes ER Stress via Interacting with THBS1/TGF‐β1 in Parkinson's Disease

“…The aberrant deposits of α‐synuclein aggregates in the brain and the degeneration of dopamine (DA) neurons are clinical manifestations of Parkinson's disease (PD) in the substantia nigra pars compacta (SNpc). [ 1 ] The hallmark motor manifestations of PD include bradykinesia (slowness of movement), rigidity, resting tremors, and postural instability, all of which significantly impact the patient's ability to carry out daily activities. [ 2 ] The most prevalent pathogeny of PD with autosomal‐dominant hereditary is leucine‐rich repeat kinase 2 (LRRK2) missense mutations.…”