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Parkinson's Disease Theraputic Landscape, : - Coggle Diagram
Parkinson's Disease Theraputic Landscape
Causes &
Indicators
molecular pathways
Dopamine Synthesis
L-tyrosine > L-DOPA (TH) > DA (DOPA decarb)
a-Syn
normally controlled by neurotrophic factors
TLR2 - Toll-like receptor2
Activated by a-Syn Oligomers
trigger microglia activation/inflammation
releases (TNF-a), IL-1beta and IL-6, chemokines, ROS, RNS
neuroinflammation
Misfolded/Abnormal Proteins
a-Syn
Gene mutations
LRRK2 - leucine rick repeat kinase2 - common
family/spontaneous - seems to regulate lysosomes - may cause LB buildup
PRKN - parkin (E3 ubiquitin ligas - mitochondria autophagy/dysfucntion in PD
PINK1 - PTEN-induces kinase 1 - same as PRKN
UCHL1
DJ-1
PTEN
GBA1
mitochondrial dysfucntion
Autophagy-Lysosome Dysfucntion
Clinical Trial / Novel Therapeutic approaches
disease modifying interventions
Targets
a-Syn
autophagy
neurodegeneration
neuroinflammation
Protien Engineering
better MAO-Bs
MRgFUS - Magnetic resonance-guided focused ultrasound ablation
ablate subthalamic nucleus, reduces movement suppression by dirupting the indirect pathway
DBS
Closed loop approaches
noninvasive
vibrotactile coordinated reset (VCR)
biomarkers
Lewy bodies (LBs)
imaging
functional
structural
Current Treatments
Alleviate motor symptoms
reinstate striatal dopamine tone
dopaminergic drugs (L-DOPA?)
MAO-B - monoamine oxidase-B
COMT - catechol-O-methyl-transferase
decarboxylase enzymes
Drawbacks
Effectiveness decreases with time
Side effects like hallucinations, cognitive impairment, dyskinesia
Drug combos
MAO-B has good safety/neuroprotective
Deep Brain Stimulation
used for LID (L-DOPA-induces Dyskenisia
Drawbacks
hardware issues
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