Table 1 Table summarizing structural and functional changes in the iLBD midbrain

Structural

 ↓ TH neurons in SNc

[3, 76, 77, 77, 78, 78, 79]

 ↓ TH-positive terminals in the striatum

[73]

Neurochemical

 ↓ Striatal TH

[71, 82]

 ↑ Oxidative damage in the SNc

[83]

 ↑ Neuroketals

[83, 84]

 Changes to iron metabolism

[85]

Autophagy

 ↓ Autophagy-associated SNARE molecules (SNAP29)

[86]

 Association of p62 with αSyn inclusions

[87]

Immunological

 ↑ TLR-2-positive microglia in the SNc

[88]

 ↑ CD68-positive microglia/macrophages in the SNc

[89]

 ↑ PAR-2-positive microglia in the anterior cingulate cortex (ACC)

[90]

 ↑ MCM2-positiv cells in the hippocampus (HC)

[88]

 Changes to expression of inflammatory and trophic molecules in the SNc and striatum

[91]

 ↑ CD8-positive T-cells in the SNc

[92]

 ↑ Angiogenesis marker a_vβ3

[89]

Synaptic

 ↓ DA synaptic terminals

[82, 93, 94]

 ↑ αSyn aggregates at presynaptic terminals

[95]

Gene Expression

 Deregulation of genetic networks associated with axon de-/regeneration, immune response, and endocytosis pathways in the SNc

[96]

 ↑ mtDNA mutation in the SNc

[97]

 Alteration of oligodendrocytes and their precursors

[98, 99]

 Transcriptomic alterations in the cortex

[100]

Proteomic

 Aberrant ApoE and low-density lipoprotein receptor-related protein 1 in SNc DA neurons

[101]

 Changes in neuropeptides and glutathione levels

[102, 103]

 ↑ Sialylation

[104]

 ↓ Sulfation

[105, 106]

Neuronal function and excitability

 ↓ FMRP

[107]

Peripheral changes

 ↑ p-αSyn in the vagus nerve

[108]

 ↓ Frequency bowel movements

[109]

 LBs in the submandibular glands, cervical superior ganglia, cervical sympathetic trunk and vagal nerves

[110]

 ↓ TH in epi- and myocardial sympathetic nerve fibers

[111]