IMMUNOTHERAPY FOR

PARKINSON'S DISEASE
(1)
Deregulated innate and adaptive immune functions is a key component of
neurodegeneration. So immunotherapy will be an important intervention to
restore the homeostatic immune brain environment. This approach can be used in
Alzheimer's disease, traumatic brain injury and stroke.

CLINICAL SIGNS
AND SYPMTOMS
By 2040. Parkinson's disease (PD) will
Due to loss of dopamine, progressive
affect 17.5 million people.
degeneration of dopaminergic neurons in
the substantia nigra pasr compacta (SNc)
and loss of efferent presynaptic ends in
the striatum.

CLASIS TREATMENT
It is not curative and consist of dopamine
replacement with agonists of dopamine
for upregulated dopamine receptors.
Lack of dopamine is primarily because of
lost pre synaptic neurons. Post synaptic
neurons show upregulation of dopamine
receptors with increased sensitivity to
dopaminergic ligands.
ROLE OF
NEUROINFLAMMATION
neuroinflammation contributes to
neurodegenerative process and disease
progression.
It is triggered by extracellular misfolded protein
accumulation released from dead and/or injured
neurons. This activated innate responses by
microglia with release of proinflammatory
mediators. Consequently adaptive immune
responses are no longer tolerant, and effector
lymphocytes prolong and propitiate more
neurodegeneration.

PATHOLOGY OF
PARKINSON'S DISEASE
Loss of nigrostriatal dopaminergic neurons with
the misfolding, oligomerization and accumulation
of apha-synuclein are the main hallmarks of PD.

In cell homeostasis, misfolded proteins are

ubiquitinated and degraded in proteasomes.
However, ubiquitin-proteasome system fails in PD,
this allows alpha synuclein ubiquitination,
misfolding, oligomerization and accumulation.
THE INNATE
This aggregates form the Lewy bodies in the
affected dopaminergic neurons. Presence of IMMUNE RESPONSE
misfolded-modified alpha synuclein underlies the
Failure of ubiquitin-proteasome to clear
neurological impairments of PD. Lewy bodies are
misfolded alpha synuclein leads to
no toxic, but oligomerization of alpha synuclein
accumulation and aggregation in the SNc,
forms toxic fibril molecules that are harmful for
leading to neurodegeneration. Then, the
membranes. This alters ion equilibrium, generates
misfolded alpha synuclein is liberated
oxidative stress and leakage of molecules.
from the neurons and triggers activation
All together provides neuron damage and death.
of microglia, promoting a
Alpha synuclein modified and oligomerized in the
proinflammatory microenvironment that
extracellular space acts as DAMPs that triggers
helps even more to neurodegenerative
innate immune responses when binding PRRs in
processes within the area of dopaminergic
microglia, macrophages, DCs.
neurons.
The oxidative stress make dopamine more
unstable (forming dopamine quinones), damage
Proinflammatory microenvironment
neurons, mitochondrial dysfunction, necrosis and
increases BBB permeability, allowing the
promote inflammation.
entrance of more innate and adaptive
The proinflammatory milieu drains to cervical
immune cells.
lymph nodes to promote adaptive inflammatory
immune responses.
 AUTOIMMUNITY IMMUNOMODULATION
immune cells within the SNc and T cell AND THERAPY
recognition of alpha synuclein derived
regulatory lymphocytes suppress immune
epitopes suggests that dopaminergic cell
responses by secretion of IL-10 and TGF-B. Promote
derived epitopes are a target for
apoptosis of effector lymphocytes and reactive
lymphocytes, suggesting an autoimmune
microglia.
response against alpha synuclein.

Treg inducer drugs are promising in

immunotherapy for PD, such histone deacetylase,
glucocorticoids, monoclonal antibodies against
CD3, etc.
Tregs with increased function stops the cycle of
neurodegeneration and neuroinflammation.

CGM-CFS is been used to induce tolerogenic DCs

and subsequent Treg populations.

ACTUAL THERAPY
APROACHES IN PD
1. Regeneration of dopaminergic lost
neurons.
2. Immunoprotection to dopaminergic
neurons to prevent cell death.

REFERENCES

1. SCHWAB AD, THURSTON MJ, MACHHI J, OLSON KE,

NAMMINGA KL, GENDELMAN HE, ET AL. NEUROBIOLOGY OF
DISEASE IMMUNOTHERAPY FOR PARKINSON ’ S DISEASE.
NEUROBIOL DIS [INTERNET]. 2020;137(OCTOBER
2019):104760. AVAILABLE FROM:
HTTPS://DOI.ORG/10.1016/J.NBD.2020.104760

MADE BY: JUAN FELIPE DUARTE ZAMBRANO

MAIL: JDUARTEZ@UNAL.EDU.CO

04/02/2021