MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Alzheimerova choroba

GSK-3 inhibitors

Https://en.wikipedia.org/wiki/GSK-3


Hericium


Polyphenols such as resveratrol (108–112), gallic acid (11, 113, 114), curcumin (115–118), anthocyanins (119), luteolin (120), hesperetin (121), genistein (122), Boswellia serrata gum extract (123), mango leaf extract (124), and flavonoids (125), exist in a variety of plants. They have various functions, such as preventing oxidative stress damage, regulating blood glucose concentration, inhibiting inflammation, improving IR, and neuroprotection, which are all beneficial to DM and AD. A great body of research have confirmed that having foods rich in polyphenols could reduce the risk of DM and AD (12), improve insulin sensitivity in DM patients to inhibit the formation of AGEs, and promote cellular uptake of glucose (126). Polyphenols could also prevent the subsequent development of DM-related complications such as cardiovascular disease, neuropathy, etc., and improve neuronal metabolism and cognitive performance (127), Carotenoids, such as lycopene have been shown having beneficial effects on diabetes and its associated complications in many animal studies, and are potentially effective drug components for the treatment of AD (128, 129).

Supplementation of trace elements, such as magnesium and zinc in diabetic patients could promote glucose transport, maintain normal cell function and lipid metabolism, and enhance tyrosine kinase activity. There was a significant negative association between magnesium intake and all-cause dementia, but the same association was not observed in AD, whereas cognitive improvement was found after zinc therapy in a mouse model of AD, indicating that zinc may play an important role in the pathogenesis of AD (130, 131).

Intake of n-3 FAs (132), pentacyclic triterpenoids (133), Hedera nepalensis crude extract and lupin alcohol (134), marine phenolics (135), fig leaf extract (136), ?-lipoic acid (137) has been shown to positively mediate inflammatory and immune responses, reduce the risk of IR and neurocognitive impairment, and ultimately decrease the risk of AD.
The effects of nutritional intervention for DM with AD mentioned above are summarized in Table 1.https://www.frontiersin.org/articles/10.3389/fnut.2022.1046726/full

Anit-aggression and other behavioural disturbances

  • Olanzapine
  • Melperone
  • Haloperidol (Nevšímalová et al., 2005, Raboch and Zvolský, 2002) [1]

Antidepresiva

  • Používaná
    • Maprotiline
    • Mianserin [1]


ApoE 2


Astrocytes

  • Recently linked to the possible role as phagocytes
  • In some cases such as after brain trauma
    • Astrocytes had been associated with the phagocytic function
      • Ability for phagocytosis was very variable in different cell populations
  • After triggering astrocyte phagocytosis by Abeta
    • Blocking CD36 by neutralizing antibody resulted in
      • Lessening Abeta -induced phagocytosis by astrocytes (Jones et al., 2013) [1]

Catalase enzym

  • Very effective in destroying the toxic concentration of hydrogen peroxide
    • Without changing its low, physiologic concentration

Decrease in catalase

  • Due to anemia
    • Decreased synthesis
  • Inherited deficiency

Důsledky

Ellagic acid - EGA

  • Commonly found in fruits

Myší model exp. STZ

  • Central administration of STZ in rodents instigates dementia - (STZ-ICV) model of Alzheimer's disease
    • Impairment of phosphoinositide 3 (PI3)-kinase-regulated endothelial nitric oxide synthase (eNOS) activity
  • Chronic administration of EGA
    • Prevents dementia through modulation of PI3-kinase-endothelial nitric oxide synthase signalling in streptozotocin-treated rats
    • EGA (35 mg/k, p.o.) for 4 weeks daily attenuated the STZ-ICV (3 mg/kg)-triggered increase of
      • Brain oxidative stress
      • Nitrite
      • TNF-? levels
      • AChE
      • LDH activity
    • Memory restoration by EGA in STZ-ICV-treated rats was conspicuously impaired by
      • N(G)-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg, 28 days)
      • Wortmannin (5 µg/rat; ICV) treatments
        • PI3-kinase inhibitor [3]

myší model exp. Arsenu

  • Ellagic acid attenuates arsenic induced neuro-inflammation and mitochondrial dysfunction associated apoptosis.
    • Inflammation and mitochondrial dysfunction in hippocampi of wistar rats
    • Rats were pre-treated with EA (20 and 40?mg/kg b.wt; p.o. for 11?days) along with arsenic (10?mg/kg; p.o. for 8?days) [4]
  • arsenic exposure
    • Increased total ROS generation and DNA fragmentation
    • Decreased mitochondrial membrane potential alongwith an increase in expression of pro-apoptotic and inflammatory markers [4]
  • EA complementation
    • Downregulated
      • Total ROS generation dose dependently
      • Apoptotic markers, BAX and Bcl2
      • Inflammatory markers, IL-1ß, TNF?, INF?
      • Attenuated effects on mitochondrial membrane potential
  • EA might substantiate to be a budding therapeutic candidate against arsenic induced neurotoxicity [4]


Extract of ginkgo biloba E 761

  • Enhance the brain metabolism
    • Oxidative metabolism of glucose [1]

Hypnotika

  • Používaná
    • Zopiclone
    • Zolpidem [1]


Inhibitors of acetylcholinesterases

  • Inhibits the activity of enzymes responsible for degradation of acetylcholine
  • Enhance cognitive functions for a brief moment [1]

Donepezil

Rivastigmine


Lecitin

  • Possible
  • Not very effective
  • Precursor of acetylcholine [1]

M1 subtype of the muscarinic-cholinergic receptor

  • Could have a neuroprotective character to some extent
  • It decreases Abeta
  • Decreases also the phosphorylation of tau protein in vivo and in vitro (Terry Jr and Buccafusco, 2003) [1]

Microglial phagocytosis

  • Regulated by receptors
    • Mainly by Tolllike receptors 2 and 4
    • Phosphatidylserine receptor
    • Scavenger receptor CD36 [1]
  • Extracellular accumulation of Abeta
    • Its clearance by phagocytosis
    • Mediated by microglial cells
      • Progress of the AD or possible treatment

Dysfunction of activation of microglia, or the microglial cells itself

  • Caused by some deficiency or age
    • May contribute to the progression of the AD (Jones et al., 2013)
  • Microglial cells
    • Known for their interaction with fibrillar amyloid beta
      • Results in the production of pro-inflammatory
        • Subsequently neurotoxic substances - reactive oxygen species
  • One of the Abeta induced proinflammatory CD36 signalling cascade
    • Start with the interaction between CD36 and Lyn kinase
      • Essential for activation of
        • Pro-inflammatory responses
        • Downstream p44/42
  • Fyn
    • Another member of Src family kinase also responsible for activation of p44/42
      • Interaction with CD36 is indirect
  • Interruption of Lyn kinase signalling
    • Reduced accumulation of amyloid beta
    • And hence the accumulation of microglia had been observed
      • Reduction of microglial accumulation observed in mice lacking the CD36
        • Important role of CD36-associated signal transduction in the inflammatory response (Moore et al., 2002)
  • CD36
    • Necessary for Abeta induced activation of macrophages and microglia
  • Scavenger receptor SR-A
    • Responsible for this adherence too
  • CD36-/- microglial cells
    • Normal adherence to the amyloid beta (El Khoury et al., 2003) [1]
  • Class B scavenger receptor CD36
    • Neuroprotective role of CD36 would be activated
      • Due to the elimination of Abeta depositions by microglial cells
  • In later stages pro-inflammatory cytokines
    • IL-1beta , IL-18 and IL-1alpha
      • Formed as a reply to Abeta aggregation
        • Will probably decrease the sensitivity of the genes responsible for the elimination of Abeta deposition
        • Leading to the accumulation of Abeta
          • Causing neurodegeneration (Šerý et al., 2017) [1]

Neuroleptics

  • For example, risperidone [1]


Ovoce a zelenina

  • Higher intake of fruits and vegetables had been associated with decreased risk of the AD [1]

Pet therapy

  • Keeping of a pet [1]

Piracetam

  • Enhance the brain metabolism
    • Oxidative metabolism of glucose [1]
  • Enhance cognitive functions for a brief moment [1]

Propentofylline

  • Neuroprotektivní [1]


Psychotherapy

  • Most effective in the early stages
  • Can help to delay the inevitable memory impairments [1]


Pyritinol

  • Enhance the brain metabolism
    • Oxidative metabolism of glucose [1]
  • Enhance cognitive functions for a brief moment [1]

Re-education techniques

  • To help the patients with everyday life [1]

Alzheimer diesease reversal

Amyloid precursor protein - APP

  • Transmembrane protein
  • Cleaved by alpha-secretase (ADAM)
    • Produces soluble sAPP alpha protein
      • Regulates proliferation of neuronal stem cells
        • Considered as neuroprotective
  • Fragments are no longer than 40 amino acids
    • Production of new synapses (Raboch et al., 2012) [1]
.app.jpg
[1]

Selegiline

  • Neuroprotektivní [1]

Social activity and cognitive engagement

  • Minimal decline in the risk had been shown in patients with more cognitive engagement and social activity (Daviglus et al., 2011) [1]

Videa na téma jak zvrátit Alzheimerovu chorobu

Knihy

  • Nepodliehajme Alzheimeru - Dr. Dale Bredesen

Neuroregenerace

O úroveň výše

Poslední aktualizace: 4. 3. 2024 20:56:10