Sex and Brain: The Role of Sex Chromosomes and Hormones in Brain Development and Parkinson’s Disease
Abstract
:1. Sex Hormones and Sex Chromosomes as Players in the Sexual Differentiation of the Mammalian Brain
1.1. Steroid Hormones in the Central Nervous System
Steroid Hormone | Activated Receptor | Functions | Targets | References |
---|---|---|---|---|
Estrogen | ERα, ERβ | Neuroprotection | Antiapoptotic genes | [20,21,22,23] |
Proliferative genes | ||||
Progesterone | PR-A, PR-B | Neuroprotection | Promyelinization genes | [24,25] |
Anti-inflammatory genes | ||||
Testosterone | AR | Neuroprotection | Remyelination process by oligodendrocytes | [26,27,28] |
Astrocyte recruitment | ||||
Sex phenotype | Development and maintenance of male phenotype in CNS | [29,30,31] |
Steroid Hormone | Activated Receptor | Functions | References |
---|---|---|---|
Estrogen | ERα, ERβ, mERs, GPER1 | Oligodendrocyte differentiation, survival, and function | [32] |
Spine plasticity | [33,34,35,36] | ||
Behavior | |||
Progesterone | PR-A, PR-B, mPRs, PGRMC1 | Female reproductive behavior | [37,38,39,40] |
Cerebellum cortical formation | |||
Neuroprotection | |||
Testosterone | AR, GPCRs | Sexual differentiation | [41,42,43,44,45,46] |
Reproductive and aggressive behaviors | |||
Neuroendocrine response |
1.2. Sex Hormones’ Modulation of Brain Sexual Differentiation
1.3. Sex Hormone-Dependent Brain Sexual Dimorphism
1.4. Sex Chromosomes’ Impact on Brain Sexual Differentiation
1.5. Epigenetic Regulation of Brain Sexual Differentiation
2. Sex-Related Differences in Neurodegeneration
2.1. Focus on Parkinson’s Disease
2.2. Sex-Related Differences in Microglia and Their Implication on Neuroinflammation in PD
2.3. Sex Bias in Parkinson’s Disease and the Role of Sex Hormones
2.3.1. Estrogens
2.3.2. Progesterone
2.3.3. Androgens
2.4. Effects of Estrogen-Based Pharmacological Treatments on Parkinson’s Disease
2.5. Contribution of Genes Located on the Sex Chromosomes to Parkinson’s Disease Etiology
2.6. Sex Differences in Immortalized and Primary Cells Relevant to Parkinson’s Disease Research
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Gene Product | Function | PD Inheritance |
---|---|---|---|
Well established | |||
SNCA | Alpha-synuclein | Synaptic vesicle exocytosis; DA neurotransmission; chaperone activity | Dominant |
LRRK2 | Leucine-rich repeat kinase 2 | Neuronal plasticity; autophagy; vesicle trafficking; neuroinflammation | Dominant |
VPS35 | Vacuolar protein sorting 35 | Membrane protein recycling | Dominant |
PRKN | Parkin | Mitochondrial quality control | Recessive |
PINK1 | PTEN-induced kinase 1 | Mitochondrial quality control | Recessive |
DJ-1 | DJ-1 | Protection against oxidative stress; mitochondrial function | Recessive |
Atypical complex PD | |||
ATP13A2 | Cation-transporting ATPase 13A2 | Lysosomal cation and polyamine transporter | Recessive |
DNAJC6 | DNAJ subfamily C member 6 | Endocytosis of clathrin-coated vesicles | Recessive |
FBXO7 | F-box protein 7 | Ubiquitination; proteasome degradation | Recessive |
SYNJ1 | Synaptojanin-1 | Synaptic vesicle endocytosis; actin filament rearrangements | Recessive |
PLA2G6 | Phospholipase A2, group 6 | Membrane homeostasis; mitochondrial integrity; signal transduction | Recessive |
Risk factors | |||
GBA1 | Glucosylceramidase beta | Lysosomal function; lipid metabolism | Risk factor |
MAPT | Microtubule-associated protein Tau | Axonal stability; axonal transport | Risk factor |
X-linked genes associated with parkinsonism | |||
RAB39B | Ras-related protein Rab-39B | Vesicular trafficking | X-linked parkinsonism |
FMR1 | Fragile X messenger ribonucleoprotein 1 | Synaptic plasticity; negative role in translation | FXTAS with parkinsonism |
TAF1 | TATA-box-binding protein associated factor 1 | Initiation of transcription | X-linked dystonia-parkinsonism |
GLUD2 | Glutamate dehydrogenase 2 | Glutamate metabolism; neurotransmission | Polymorphism |
PD Model | Effect | Phenotype |
---|---|---|
Acute MPTP model | Inhibition of complex I | Motor deficit; DA neuron death; No α-syn aggregates. |
Subacute/chronic MPTP model | Inhibition of complex I | Progressive model; No motor deficit; No DA neuron death; α-syn aggregates. |
6-OHDA | Inhibition of complex I and oxidative stress | Asymmetric motor deficit; DA neuron death; No α-syn aggregates. |
Rotenone | Inhibition of complex I | Limited motor deficit; Moderate DA neuron death; α-syn aggregates. |
Paraquat | Oxidative stress | Limited motor deficit; Limited DA neuron death; α-syn aggregates. |
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Terrin, F.; Tesoriere, A.; Plotegher, N.; Dalla Valle, L. Sex and Brain: The Role of Sex Chromosomes and Hormones in Brain Development and Parkinson’s Disease. Cells 2023, 12, 1486. https://doi.org/10.3390/cells12111486
Terrin F, Tesoriere A, Plotegher N, Dalla Valle L. Sex and Brain: The Role of Sex Chromosomes and Hormones in Brain Development and Parkinson’s Disease. Cells. 2023; 12(11):1486. https://doi.org/10.3390/cells12111486
Chicago/Turabian StyleTerrin, Francesca, Annachiara Tesoriere, Nicoletta Plotegher, and Luisa Dalla Valle. 2023. "Sex and Brain: The Role of Sex Chromosomes and Hormones in Brain Development and Parkinson’s Disease" Cells 12, no. 11: 1486. https://doi.org/10.3390/cells12111486